EXCITED STATES FREE RADICALS REPAIR CLONOGENICITY LETHALITY
-MUTATION CARCINOGENESIS AGEING HAZARDS RISK ASSESSMENT ^ CANCER THERAPY
International Journal of RADIATION BIOLOGY and related studies in Physics, Chemistry and Medicine
Editor: D A V I D SCOTT
Associate Editors: J O L Y O N H . H E N D R Y and E D W A R D J . L A N D
Editorial Office: Paterson Institute for Cancer Research, Christie. Hospital & Holt Radium Institute, Manchester M20 9BX
Editorial G. E. Adams, U.K. G. Ahnström, Sweden K . - D . Asmus, F . R . G e r m a n y R. R. Atayan, U.S.S.R. D . Averbeck, F r a n c e E. Ben-Hur, I s r a e l N. M . Bleehen, U.K. J. J. Broerse, The N e t h e r l a n d s P. Bryant, U.K. J. Cadet, F r a n c e M. Edgren, Sweden M. M . Elkind, U.S.A. S. B. Field, U.K. J. F. Fowler, U.K. G. B. Gerber, B e l g i u m D . T . Goodhead, U.K. M . N. Gould, U.S.A. G. R. ter Haar, U.K. D . G. Harnden, U.K. K. Held, U.S.A. T. Hermann, G . D . R . D Kessel, U S A . J. Kiefer, F . R . G e r m a n y C. J. Koch, C a n a d a
Board ~Ä.~ W. T. Konings, The N e t h e r l a n d s A. Lehmann, U.K. J. B. Little, U.S.A. H. Loman, The N e t h e r l a n d s S, Okada, J a p a n N. L. Oleinick, U.S.A. R. B. Painter, U.S.A. M. Quintiliani, I t a l y I. R. Radford, A u s t r a l i a J. L. Redpath, U.S.A. R. Saunders, U.K. Shen Xun, C h i n a G. Silini, A u s t r i a B. B. Singh, I n d i a C. von Sonntag, F.R. G e r m a n y G. GL Steel, U.K. I. Szumiel ,Poland A. Tallentire, U.K. D . M . Taylor, F . R . G e r m a n y H. D . Thames, U.S.A. H. Utsumi, J a p a n P. Wardman, U.K. R. L. Warters, U.S.A. G. F. Whitmore, C a n a d a
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International Journal pf RADIATION BIOLOGY
and related studies in Physics, Chemistry and Mq£ifin$l t g §
Taylor & Francis, London, New York, Philadelphia
Vol. 52 No. 6 December 1987
Contents
Editorial . . . . . . . . . . ... 825
REVIEW Interactioh of faetors modifying the radiosensitivity of dormant seeds:
A review R. R. Atayan . . . . 827
RAPID COMMUNICATIONS A radioprotector: cysteamine, inhibits oxygen transport in lipidic
membranes: A. Vachon, V. Roman, C. Lecomte, G. Folcher, M . Fatöme, P. Braquet and F. Berleur . . 847
Use of'nuclear monolayers'to identify faetors influencing DNA double-strand breakage by X-rays. L R . Radford . . 853
LOW DOSE AND DOSE RATE Absenee of a dose-rate effect in the transformation of C3H 10T1/2 cells by
a-particles. L. Hieber, G. Ponsel, H . Roos, S. Fenn, E. Fromke and A. M . Kellerer . 859
P L U T O N I U M The effect of 2 3 8 P u a-particles on the mouse fibroblast cell line C3H
10T1/2: characterization of source and RBE for cell survival. C. J . Roberts and D. T. Goodhead 871
Diflferences in the uptake of transferrin bound 2 3 9 P u and 5 9 Fe into multicellular spheroids of hepatocytes from adult male rats. F. Schuler, C. Csovcsics and D. M . Taylor 883
DNA D A M A G E The relationship between radiation-induced DNA double-strand breaks
and cell kill in h^mster V79 fibroblästs irradiated with 250 kVp X-rays, 2*3 MeV neutrohs or 2 3 8 P u a-particles. K. M . Prise, S. Davies and B. D. Michael 893
FRACTIONATION The kinetics of repair in mouse lung after fractionated irradiation.
E. L. Travis, H. D. Thames, T. L. Watkins and I. Kiss 903
SENSITIZATION Radiation sensitization of E . c o l i B/r by mixtures of oxygen and nitrous
oxide. D.Ewing . . 921
HYPERTHERMIA Interaction of whole-body hyperthermia and irradiation in the treatment
of AKR mouse leukemia. R. A. Steeves, H . I. Robins, K. Miller, P. Martin, L. Shecterle and W. Dennis 935
VIRUSES Activation of endogeneous retroviruses in mouse cells by thermal
neutrons. O. Niwa, T. Saigusa, T. Ikushima and T. Sugahara 949
conünues inside
RADIONUCLIDES Evaluation of radiation dose resulting from the ingestion of [ 3 H ] - and
[14C]thymidine in the rat. H . Takeda and T. Iwakura 957
Letter to the editor Does initial haemoglobin level modify the efficacy of radiosensitizers? An
analysis of the M R C Misonidazole studies in head and neck Cancer and cervix Cancer. M R C Sensitizer Advisory Group 965
Meeting Statement Statement from the 1987 Como meeting of the International Commission
on Radiological Protection . . . . 969
Book Reviews Fractionation in Radiotherapy. By H . D. T H A M E S and J . H . H E N D R Y
(Reviewed by J. Dutreix) 975
The C h e m i c a l Basis of R a d i a t i o n B i o l o g y . By C. V O N S O N N T A G (Reviewed byP.O'Neill) . . . . . . . . . . 975
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Absence of a dose-rate effect in the transformation of C3H 10T1/2 cells by a-particles
L . H I E B E R , G . P O N S E L , H . R O O S , S. F E N N , E . F R O M K E , and A . M . K E L L E R E R
Institut für Medizinische Strahlenkunde, Universität Würzburg , D 8700 W ü r z b u r g , F R Germany
( S e c o n d v e r s t o n r e c e i v e d 2 4 J u l y 1 9 8 7 ; a c c e p t e d 1 4 A u g u s t 1 9 8 7 )
The findings of H i l l et a l . (1984) on the greatly enhanced transformation frequencies at very low dose rates of fission neutrons induced us to perform an analogous study with a-particles at comparable dose rates. Transformation frequencies were determined with y-rays at high dose rate (0-5 Gy/min) , and with a-particles at high (0-2 Gy/min) and at low dose rates (0-83-2-5 mGy/min) in the C 3 H 10T1/2 cell System.
a-particles were substantially more effective than y-rays, both for cell inactivation and for neoplastic transformation at high and low dose rates. The relative biological effectiveness (RBE) for cell inactivation and for neoplastic transformation was of similar magnitude, and ranged from about 3 at an a-particle dose of 2 G y to values of the order of 10 at 0-25 G y . In contrast to the experiments of H i l l et a l . (1984) with fission neutrons, no increased transformation frequencies were observed when the a-particle dose was protracted over several hours.
1. Introduction Exper iments on oncogenic t ransformat ion have been per formed i n a variety of
cel l Systems and w i t h different i o n i z i n g radiations. Extensive Information has been obta ined for sparsely i o n i z i n g radiations, such as
y- and x-rays, e.g. by Borek and H a l l (1973), T e r z a g h i and L i t t l e (1976), M i l l e r et a l . (1979), H a n et a l . (1980), M i l l e r and H a l l (1978), and others; for densely i o n i z i n g radiat ion data are more l i m i t e d . F o r a-part icles results have been g iven by Rober t son et a l . (1983) for B a l b / c 3 T 3 cells, and by L l o y d et a l (1979) and H a l l and H e i (1985) for C 3 H 1 0 T 1 / 2 cells . Y a n g et a l . (1985) have reported data for heavy ions of intermediate to h i g h L E T . T h e r e have also been a number of studies w i t h neutrons (Borek et a l . 1978, Barendsen and Ga i se r 1985). O f par t icular importance are the results of H i l l , E l k i n d and co-workers, w h o found that smal l doses of fission neutrons have greatly increased t ransformation efficiency when they are appl ied at l ow dose rates ( H i l l et a l . 1984) or fractionated over several hours ( H i l l et a l . 1985). The Potential implications of these results and the tentative nature of attempted explanations led us to perform similar experiments w i t h other densely i o n i z i n g radiations, and a-part icles seemed to be a suitable moda l i ty that w o u l d pe rmi t h igh ly controlled experimental condi t ions .
2. Materials and methods 2.1. C e l l c u l t u r e a n d i r r a d i a t i o n p r o c e d u r e s
T h e studies were pe r formed with the C 3 H 1 0 T 1 / 2 mouse-embryo fibroblasts System developed by R e z n i k o f f et a l . (1973). O u r cells were f rom the ce l l stock of Hall and M i l l e r transfered in 1981 to the G S F , M ü n c h e n , and k i n d l y subcu l tu red for us
860 L . H i e b e r et a l .
by D r R . T r o t t . T h e cells were mainta ined i n Eagle 's basal m e d i u m supplemented w i t h 10 per cent heat-inactivated fetal bovine serum ( B i o c h r o m , Be r l i n ) , 50 u / m l p e n i c i l l i n , and 50jug/ml s t rep tomycin ( B R L , K a r l s r u h e ) . C e l l s o f passage 12 were cu l tu red i n 75 c m 2 flasks (Falcon) and incubated i n a h u m i d i f i e d gas atmosphere (95 per cent air, 5 per cent C 0 2 ) at 3 7 ° C . T h e p la t ing efficiency of con t ro l cultures was between 20 and 30 per cent. T w e n t y - f o u r hours before the exposures the cells were plated i n 25 c m 2 flasks for y- i r rad ia t ion , or i n special dishes cons is t ing of a glass r ing of 5 c m diameter and a fo i l bo t tom of 2 p i m thickness (Hos t aphan , K a l l e C h e m i e Wiesbaden) for a- irradiat ion. I n order to avoid settlement at the edge of the dishes where they may not be reached b y the a-particles, cells were plated only i n the centre area (3-8 c m diameter) w i t h a smal l amount of m e d i u m (0-5 m l ) . T h r e e hours later, w h e n the cells were attached, 4-5 m l of cul ture m e d i u m were added. T h e beginning of the i r radia t ion , bo th for the low dose-rate and h igh dose-rate experiments, was 24 ± 2 h after p la t ing .
D ü r i n g the t ime of i r radia t ion the cells were in exponent ia l g rowth . T h i s was verified by (a) g rowth curves, (b) flow-cytometry measurement o f the D N A content, and (c) the de terminat ion of cells i n S-phase by l abe l l ing w i t h [ 3 H ] t h y m i d i n e ( 3 7 k B q / m l , 20 min ) .
T h e g rowth curves were exponent ia l f rom about 10 to 12 h after pla t ing, up to at least 48 h . T h e d o u b l i n g t ime was about 18 h .
B y f low-cytometry measurement of the D N A content the ce l l cycle d i s t r ibu t ion was determined at different t imes after p la t ing . A t 8 h , 64 per cent o f the cells were i n G l -, 18 per cent in S- and 18 per cent in G 2 + M - p h a s e ; subsequent ly the fradction of G l -phase cells decreased and the fraction of S-phase cells increased. A t least f rom 20 to 40 h , there was a constant ce l l -cycle d i s t r ibu t ion of 41 per cent G l -, 38 per cent S- and 21 per cent G 2 4 - M - c e l l s .
T h e label l ing index increased f rom about 30 per cent at 4 h to 45 per cent at 15 h after p la t ing; afterwards it remained constant at roughly 40 per cent, up to at least 40 h . T h e g rowth characteristics were equal i n the flasks and the special dishes. A t the beg inn ing of the exposures the cel l density was about 1 0 4 / c m 2 .
G a m m a - r a y exposures were f rom a cobalt-60 uni t at a dose rate of 0-5 G y / m i n . F o r the a-particle exposures the cells were irradiated f rom an amer ic ium-241 source (a disc of 85 m m diameter w i t h 0-37 G B q ) th rough the bo t tom foi l of the dishes w h i c h were posi t ioned on the exit fo i l (figure 1). T h e highest dose rate was 0*2 G y / m i n . T h e lower dose rates were achieved by micro-f rac t ionat ion , i.e. by per iod ic br ief opening (0*66 s) of a compute r -con t ro l l ed metal-disc shutter (see figure 1;6). T h e dose per microf rac t ion was 2 - 2 m G y . F o r dose rates of 2-5, 1-7 and 0-83 m G y / m i n the fractions were separated b y 50 ,102, and 154 s, respectively. O n thebasis ofmeasured nuclear cross-sections (mean value 250 jum 2) the frequency o f a-particles t raversing the cel l nucleus was calculated to be about 1 1 / G y , i.e. one out of 40 cells was hit in its nucleus per microf rac t ion .
T h e most l ike ly energy of a-particles emerging from the bo t t om foil was 2-7 M e V (see figure 2), their dose mean L E T was 147 k e V / ^ m and their frequency mean 144keV/jUm. T h e relat ively nar row energy d i s t r ibu t ion and very na r row L E T -d is t r ibu t ion was due to a h i g h degree of co l l ima t ion ; the co l l ima to r o f the a-irradiator has Channels o f length 15 m m and Channel diameters of 3 m m . T h e track-etch d iagram i n figure 3 confirms the absence of ob l ique ly inc ident a-particles. F i g u r e 4 shows the enhancement o f L E T w i t h increasing penetrat ion of the a-particles into the ce l l . T h e absorbed dose is determined as the average over 2 [ i m depth of
C e l l t r a n s f o r m a t i o n by < x - p a r t i c l e s 861
1 1
9 <L)
r r
Figure 1. Diagram of the a-irradiation device: 1: 2 4 1 A m Source (0-37 GBq) , 2: collimator, 3: exit foil, 4: incubation Chamber, 5: thermal insulator, 6: shutter, 7,8: wobble axes, 9: rotating source disc, 10: source Chamber fiushed with helium.
E N E R G Y / M e V
Figure 2. Measured spectra of the energy of a-particles after traversal of the exit foil (solid line) and after additional traversal of the bottom foil (Hostaphan, an equivalent of mylar) of a culture dish (dotted line).
862 L . H i e b e r et al .
Figure 3. Comparison of C 3 H 10T1/2 cells at density 10 4 / cm 2 with the distribution of a-particles at a dose of O l 25 G y . Panel A: 400 f i m x 275 field of an etched C R 39 foil exposed to an a-particle fluence of 5-4 x 10 5 / cm 2 , corresponding to a dose of 0125 G y . This is calculated to correspond roughly to 1-3 a-particles per cell nucleus. Panel B : 400 f i m x 275 /xm field with C 3 H 10T1/2 cells from a 24 h culture with the cell density of 10 4 / cm 2 .
C e l l t r a n s f o r m a t i o n by a - p a r t i c l e s 863
Penetrat ion. T h e y-ray con t r ibu t ion was less than 0 0 1 per cent o f the a-part icle dose. D ü r i n g the exposure the cells were he ld i n a Chamber w i t h temperature adjusted
tQ 3 7 ° C , and wi th gas flow of 6 per cent C 0 2 and 94 per cent air to achieve op t ima l p H and growth condi t ions . M o r e detailed informat ion on the a- i r radiator is g iven elsewhere (Roos and K e l l e r e r 1986).
2.2. S u r v i v a l a n d t r a n s f o r m a t i o n assay After i r radia t ion the cells were t ryps in i zed and cel l densities were de te rmined
w i t h a Cou l t e r Coun te r . I f more than about 1 0 5 cells were necessary for the t ransformation and the surv iva l assay at a specified dose—especial ly at h igher doses—two or three dishes were i r radiated successively. F o r the h i g h dose-rate experiments the two or three dishes were t ryps in i zed together and pooled . F o r low dose-rate experiments the cells f rom every d i sh were always plated separately. F o r the surviva l assay the numbers of plated cells were chosen to attain about 80 viable cells per 25 c m 2 flask. T h e flasks were incubated for 10 days. Af te r s ta ining w i t h 10 per cent G i e m s a , colonies w i t h more than 50 cells were counted as surv ivors . F o r the t ransformation assay the cells were plated in 25 c m 2 flasks w i t h about 300 viable cells per flask. A t h igh doses the numbers of v iable cells were lower , because of the lower s u r v i v i n g fraction, and not more than 20 000 cells per flask were plated i n order to avoid feeder effects. T h e cells were incubated for 6 weeks; after an incuba t ion t ime o f 2 weeks, w i t h no m e d i u m change, they reached confluency, and were then re-fed once a week. F o r the determinat ion of t ransformed foci the cul tures were washed w i t h phosphate-buffered saline, fixed w i t h methanol , and stained w i t h 10 per cent G i e m s a . O n l y foci of type 2 and 3, as descr ibed by Rezn ikof f et a l . (1973), were scored as transformants.
3. Results 3.1. I n a c t i v a t i o n by y - r a y s a n d a - p a r t i c l e s
T h e surv iva l re lat ion of C 3 H 1 0 T 1 / 2 cells after exposure to y-rays has a p ronounced Shoulder (figure 5). T h e curve corresponds to a fit of the natural
864 L . H i e b e r et al .
i i — i — i — i i i i i i i i i i i •
0 2 4 6 8
DOSE / Gy
Figure 5. Inactivation of C 3 H 10T1/2 cells by y-rays (closed circles) and a-particles (open circles) at high dose rates. The surviving fractions, S(D), at low dose rates are not significantly different from the fitted curve (S(0-25 Gy) = 0-61; S(0-5 Gy) = 0-39; S(0-75Gy) = 0-25).
logar i thm of su rv iva l to a l inear-quadrat ic dependence w i t h the coefficients a = 0 1 4 2 / G y and jS = 0 - 0 4 8 / G y 2 .
Inact ivat ion by the densely i o n i z i n g a-particles fol lows, d o w n to a s u r v i v i n g fraction of about 0-05, an exponent ia l relat ion. A t higher doses the s u r v i v i n g fraction levelled off to about 0-001. T h e ta i l of the surv iva l curve may be due to unattached mi to t i c cells not reached by the a-particles.
A t low dose rates there was no detectable change in surv iva l ; the data for h i g h and low dose rates are fitted by the same relation wi th a= 1 - 6 5 / G y .
3.2. O n c o g e n i c t r a n s f o r m a t i o n by y - r a y s a n d a - p a r t i c l e s Tab le 1 shows the data for t ransformation after exposure to a-particles at h i g h and low dose rates. T h e su rv iv ing fractions were taken from the surv iva l relations in figure 5; for doses of 2*5 and 3-0 G y the estimates were interpolated f rom observed fractions. T h e mean number of foci per flask was estimated f rom the total n u m b e r , ra, of foci and the number , M , of flasks:
X = m\M±jm\M (1)
T w o flasks were assigned one focus on ly because their n u m b e r of foci (10 and 11 at doses of 0-25 G y and 1-0 G y , respectively) were i n evident conflict w i t h a Po isson d i s t r ibu t ion . W i t h this correct ion the dispers ion, A (sample variance d i v i d e d by the mean), was not indicat ive of a systematic overdispers ion ( A > 1 ) ; it therefore appeared just if ied to base the estimates on the total number of observed foc i .
However , the choice of the estimate is not c r i t i ca l . T a b l e 2 gives the results based on the ' n u l l me thod ' of H a n and E l k i n d (1979) w h i c h ut i l izes only the ratio o f the
C e l l t r a n s f o r m a t i o n by a - p a r t i c l e s 865
Table 1. Transformation rates after exposure of C 3 H 10T1/2 cells to a-particles at low and high dose rates.
D \ absorbed dose rate, D \ absorbed dose, S: surviving fraction (values from the fitted curve in figure 5, except at 2-5 and 3-0 G y , where observed fractions are used), N s \ survivors per flask, M \ number of flasks, m: number of foci, X\ foci per flask, t\ transformation frequency per 10 4 survivors with Standard error (SE).
Table 2. Transformation rates obtained from the modified estimate (equation 2).
D : absorbed dose rate, D : absorbed dose, n : number of flasks without foci, A: dispersion, X\ foci per flask (modified estimate), t: transformation frequency per 10 4 survivors with Standard error (SE).
866 L . H i e b e r et a l .
number , n , of flasks wi thou t foci to the total number , M , of flasks and thereby avoids any bias due to satellite colonies. T h e s e estimates, w i t h their somewhat larger Standard errors (see B a l c e r - K u b i c z e k et a l . 1987):
X = - \ n { n j M ) ± J\jn-\iM (2)
are i n general agreement w i t h the data i n table 1. A s shown i n figure 6, a-particles induce transformations substantial ly more
effectively than y-rays. T h e R B E for t ransformat ion varies f rom about 3 at 2 0 G y to somewhat larger values at low doses. These R B E values are not inconsistent w i th the values of 2-3 to 9 obtained by H a l l and H e i (1985). T h e y are somewhat higher than values reported by Rober t son et a l . (1983) for B a l b / c 3 T 3 cells . T h e y-ray data, w h i c h were not a m a i n objective of this s tudy, are s t i l l subject to considerable uncertainties, and they are therefore not fitted to a numer i ca l re lat ion.
T h e results for h i g h dose-rates of a-part icles are, i n figure 7, compared to those for low dose rates. T h e r e is no evidence of increased t ransformat ion frequencies at low dose rates. T h e broken l ine corresponds to a l inear-quadrat ic relat ion for the number , T , of transformants per 1 0 4 su rv ivors :
T = 0-01 +2-9 D / G y + SA ( D / G y ) 2 (3)
T h e so l id curves pe rmi t a compar i son w i t h the results obta ined for fission neutrons
0.1 1 DOSE / Gy
10
Figure 6. Transformation frequencies per surviving cells after y- (closed circles -and a-irradiation {open circles) at high- dose rates. The broken curve corresponds to equation (3).
C e l l t r a n s f o r m a t i o n by a - p a r t i c l e s 867
DOSE / Gy
Figure 7. Transformation rates after exposure to a-particles at different dose rates: ( • ) 0-83 mGy/min , ( • ) 1-7mGy/min, ( • ) 2-5mGy/min, and (O) 0-2 Gy /min . The broken curve corresponds to equation (3). The solid curves represent the relations obtained by H i l l et a l . (1984) for their data at high dose rate (lower curve) and at low dose rate (upper curve) of fission neutrons.
by H i l l et a l . (1984). T h e i r data for h igh dose rates (lower so l id curve) are close to the dependence for a-particles. T h e Upper so l id curve represents the greatly enhanced transformation frequencies found by H i l l et a l . at l ow dose rate (0-86 m G y / m i n ) of neutrons. It is evident that there is no comparable effect i n the a-particle experiments.
4. Discussion T h e results of H i l l et a l . (1984) were h igh ly unexpected i n v iew of accepted
b iophys ica l considerations (Barendsen, 1985), and they are of sufficient pragmat ic importance that analogous investigations w i t h other densely i o n i z i n g radiations are mandatory . T h e present study has been designed to paral lel closely the experiments of H i l l et a l . (1984), so that any differences in the results w o u l d reflect differences in the effectiveness of the radiations.
U p to now there have been on ly tentative explanations (Ross i and K e l l e r e r 1986, B u r c h and Chesters 1986, E l k i n d and H i l l 1986) of the dose-rate effects, or of the analogous results wi th fractionated neutron exposures ( H i l l et a l . 1985). T h e results for a-particles appear to exclude these explanations and there is no obvious reason why the somewhat more densely i o n i z i n g a-particles shou ld not show, at a l l , a phenomenon w h i c h is so s t r ik ing ly present w i t h neutrons. Nevertheless one must note certain differences between the radiat ions.
E v e n t frequencies are larger i n the neut ron experiments . A s poin ted out earlier (Ross i and K e l l e r e r 1986), there are about s ix recoi l particles i n the nucleus of a 10T1 j 2 ce l l at a dose of 100 m G y of fission neutrons. T h i s is substantial ly more than the n u m b e r of about 1 1 a-particles t raversing the nucleus at a dose of 100 m G y i n our exper iments . If, for example, the dose-rate effect were caused b y a short phase i n the ce l l cycle of greatly enhanced sensi t ivi ty (Ross i and K e l l e r e r 1986) one w o u l d nevertheless expect to see the effect at h igher a-particle doses where there are m u l t i p l e events in the cell and its nucleus.
868 L . H i e b e r et a l .
W h i l e this has not been considered in proposed models , there migh t be an influence of the fact that neutrons produce a more var ied spec t rum of moderately h i g h and h igh L E T than the a-particles. Fu r the rmore it migh t be of impor tance that the r ä n g e of some of the neutron recoils, and par t icu lar ly the heavier recoils, are shorter than the dimensions of the cel l nucleus. A n o t h e r difference is that the a-exposures are v i r tua l ly free of an accompanying y-ray component , whi le such a component is always present w i t h neut ron i r radiat ions . A l t h o u g h there is at present no evidence that a con t r ibu t ion of y-rays can account for a sensi t izat ion o f the cells i n the low dose-rate experiments w i t h densely i o n i z i n g radiations, we have ini t ia ted l im i t ed experiments to investigate this aspect. In one group of three experiments at low dose rate w i t h a-particle doses of 0-25, 0-5, and 0-75 G y a y - c o n t r i b u t i o n of about 4 per cent (from a smal l caesium-137 source) was appl ied s imul tanous ly . T h e observed t ransformation rates (wi th a total number o f on ly three transformants) were insignif icant ly lower than those obtained i n the low dose-rate experiments wi thou t the y-component . In a further group of two experiments at a-doses of 0*25 and 0*75 G y an equal dose of y-rays f rom a cobalt-60 source was adminis te red in s ix fractions d u r i n g the a-exposures; the result of these c o m b i n e d exposures (with a total number of six transformants) was again not larger than the rates seen i n the a-particle exposures at 0-25 and 0-75 G y .
T h e a-particle doses were appl ied i n mu l t i p l e fractions of 2*2 m G y . H o w e v e r , this should be of no consequence since each of the cell nuc le i experiences an a-particle i n only about 1 out of 40 fractions. E v e n for the whole ce l l the number o f particles per fraction is less than un i ty (for i l lus t ra t ion see figure 3).
It is uncertain whether any remain ing differences i n the exper imenta l procedure migh t contr ibute to the differences i n the observed results. A discrepancy between our experiments and those of H i l l et a l . (1984) lies i n the fact that we exposed the cells at somewhat higher densities ( roughly 1 0 4 / c m 2 ) , i n order to ob ta in a sufficient number of a-irradiated cells. Howeve r , as emphasized, a n u m b e r of cr i ter ia have been evaluated to ascertain that the cells were i n asynchronous g rowth at the t ime of i r radia t ion.
H i l l et a l . (1984, 1985) have pointed out that their Observation are i n l ine w i t h certain i n v i v o studies, w h i c h indicate a s imi la r reversed dose-rate effect for neutrons. T h e absence of an analogous result in our studies w i t h a-particles mus t therefore not detract f rom the importance of the earlier studies. Instead it appears desirable to extend the investigations to other radiat ion modal i t ies .
Acknowledgments T h i s work was suppor ted by the Deutsche Forschungsgemeinschaf t ( D F G ) ,
Sonderforschungsbereich 172, C - l . W e are indebted to D r M o r t i m e r M . E l k i n d for his c r i t ica l comments on the manuscr ip t and his helpful suggestions. W e are also par t icular ly grateful to our colleague D r H e i k e W u l f , who had begun the cel l t ransformation studies at the laboratory.
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iNT. j . RADIAT. RIOT.., 1987, V O L . 52, N O . 6, 983-991
I N D E X O F A U T H O R S (with titles)
PACK
Ahe, M . , see Shibamoto, Y . Abelidis, S., Moore, J . S., and Chakravarty, A . : Zinc release from irradiated yeast
alcohol dehydrogenase . . . . . . . . . . . 4 1 3 Adams, G . E . , see Wall ing, J . M . Adams, G . E . D . , see Freedman, L . S. Adelstein, S. j . : Meeting report: International Workshop on D N A Damage by Auger
Emitters: Implieations and Application . . . . . . 8 1 4 Albert ini , G . , Fanelli, E . , Guidoni , L . , lanzini, F., Mariani , F., Masella, K. ,
Rustichelli, F. , and V i t i , V . : Studies of structural modifications induced by y -irradiation in distearoylphosphatidylcholine liposomes . . . . 1 4 5
Anderstam, B. , see Harms-Ringdahl, M . Armstrong, D . A . , see Surdhar, P. S. Asmus, K . - D . , see Mönig, J . Atayan, R. R.: Interaction of factors modifying the radiosensitivity of dormant seeds:
A review . . . . . . . . . . . . . . 827 Atlante, A . , see Moreno, G . Austen, K . R. J. , Jenner, T . J . , O ' N e i l l , P., and Fielden, E . M . : Variation of the
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Averbeck, D . , see Dardalhon, M . Awa, A . A . , see Ban, S.
Balla, I., Miche l , C . , and Fr i tz -Niggl i , H . : Synergistic interaction between vindesine and X-rays in the prenatal development of mice . . . . . . 371
Balzi, M . , see Becciolini, A . Ban, S., Iida, S., Awa, A . A . , and Sawada, S.: Lethal and mutagenic effects of 2 ' v 2 l ' t '
radiation in cultured human cells . . . . . . . . . 245 Baugnet-Mahieu, L . , see Grinfeld, S. Baumgärtel , H . , see Ehrl ich, W . Beauvallet, M . , see Fritsch, P. Beauvallet, M . , see Fritsch, P. Becciolini, A . , Porciani, S., Lanin i , A . , and Balzi, M . : Polyamine content as a marker
of radiation injury in the rat spieen . . . . . . . . . 767 Becker, W . , see Dikomey, E . Berleur, F . , see Vachon, A . Berteaud, A . J . , see Dardalhon, M . Bettega, D . , Calzolari, P., and Lombardi , L . T . : Effects of split-dose irradiation on
survival and oncogenic transformation induced by 31 M e V protons in C3H10T1/2 cells 761
Birch, I). A . : see Bryant, P. E . Bjerring, P.: Intratumoural light distribution in an experimental mouse tumour
irradiated by a diffuse-light irradiator compared with unilateral helium-neon light for photodynamic therapy . . . . . . . . . . . 1 9 1
Bleehen, N . M . , see Freedman, L . S . Bobrowski, K . , and Holcman, J. : Formation of three-electron bonds in one-electron
oxidized methionine dipeptides: a pulse radiolytic study . . . . . 1 3 9 Bonincontro, A . , Cametti, C . , Rosi, A . , and Sportelli. L . : Alteration of membrane
conduetivity and fluidity in human erythrocyte membranes and erythrocyte ghosts following gamma-irradiation . . . . . . . . . . 447
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984 I n d e x of a u t h o r s { w i t h t i t l e s )
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Braquet, P., see Vachon, A . Brenner, D . J . : Letter to the Editor: Concerning the nature of the initial damage
required for the production of radiation-induced exchange aberrations . . 805 Brizgys, L . M . , see Warters, R, L . Bryant, P. E . , Birch, D . A . , and Jeggo, P. A : High chromosomal sensitivity of Chinese
hamster xrs 5 cells to restriction endonuclease induced D N A double-strand breaks 537 Bubenikovä, D . , see Svoboda, V . Bush, C , see Schlappack, O. K .
Calzolari, P., see Bettega, D . Cameron Mitchel l , J . , and Norman, A . : The induction of micronuclei in human
lymphocytes by low doses of radiation . . . . . . . . 5 2 7 Cametti, C , see Bonincontro, A . Camplejohn, R. S., see Penhaligon, M . Carsten, A . L . Book review . . . . . . . . . . . 8 2 1 Chakravarty, A . , see Abelidis, S. Chan, P. K . L . , Skov, K . A . , and James, B. R.: Further studies on toxic and
radiosensitizing properties of ruthenium complexes of 4-nitroimidazoles . . 49 Clark, A . W. , see Yatvin, M . B. Clarkson, J. M . , see Mitchel l , D . L . Courteille, F . , see Fatome, M . Courtenay, V . D . , see Penhaligon, M . Csovcsics, C , see Schuler, F .
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effects of 2-45 G H z microwaves on survival and viability of Chinese hamster V-79 cells . . . . . . . . . . . . . . . 325
Darden Jr., E . B . , see Friedberg, W . Davids, J . A . G . , see Gasinska, A . Davies, S., see Prise, K . M . Davies, S. E . , see O ' N e i l l , P. O. De Haas, M . P., see Visscher, K . J . De Ruiter-Bootsma, A . , see Gasinska, A . Deal Jr, R. B . , see Friedberg, W . Dean, S. W . : Some aspects of glutathione metabolism in ataxia-telangiectasia
fibroblasts . . . . . . . . . . . . . . 43 Delic, J . I., see Schlappack, O. K . Dennis, M . F . , see Watts, M . E . Dennis, W . , see Steeves, R. A . Dikomey, E . , Becker, W . , and Wielckens, K . : Reduction of DNA-polymerase ß
activity of C H O cells by single and combined heat treatments . . . . 7 7 5 Dische, S., see Freedman, L . S. Dutreix, J . Book review . . . . . . . . . . . . 975
F^ady, J. J. , see Stephens, T . C . Eckardt-Schupp, F . , see Frankenberg, D . Eguchi, K . , Inada, T . , Yaguchi, M . , Satoh, S., and Kaneko, I.: Induction and repair
of D N A lesions in cultured human melanoma cells exposed to a nitrogen-ion beam 115 Ehrl ich, W . , Mangir , M . , Nothelfer, R. , Baumgärtel , H . , and Lochmann, E . - R . :
Thiopyronine-sensitized photodynamic effect on cell growth, R N A and D N A synthesis of Chinese hamster ovary cells . . . . . . . . . 207
Erben-Russ, M . , Bors, W. , and Saran, M . : Reactions of linoleic acid peroxyl radicals with phenolic antioxidants: a pulse radiolysis study . . . . . . 393
Ewing, D . : Radiation sensitization of E . c o l i B/ r by mixtures of oxygen and nitrous oxide . . . . . . . . . . . . . . . 921
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Fanelli, E . , see Albert ini , G . Farrell, N . P., see Skov, K . A . Fatome, M . , Courteille, F . , Laval , J . D . , and Roman, V . : Radioprotective activity of
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stationary magnetic field—the case of thymidine kinase in mouse bone marrow cells 469
Feinendegen, L . E . , see Schneeweiss, F . H . A . Fenn, S., see Hieber, L . Feola, J . M . , see Goud, S. N . Fielden, E . M . , see Austen, K . R. J . Folcher, G . , see Vachon, A . Folkard, M . , see Gasinska, A . Forn i , L . G . , see Mönig , J . Fowler, J . F . , see Gasinska, A . Frankenberg, D . , Kistler, M . , and Eckardt-Schupp, F . : Effect of cellular glutathione
content on the induction of D N A double Strand breaks by 25 M e V electrons . 185 Frankenberg, D . , see Frankenberg-Schwager, M . Frankenberg-Schwager, M . , Frankenberg, D . , and Harbich, R.: Possible occurrence
of D N A double-strand breaks during repair of u.v.-induced damage in yeast . 107 Freedman, L . S., Honess, D . J . , Bleehen, N . M . , Adams, G . E . , Dische, S., and Henk,
J. M . : Letter to the Editor: Does initial haemoglobin level modify the efncacy of radiosensitizers? A n analysis of the M R C misonidazole studies in head and neck cancer and cervix cancer . . . . . . . . . . 965
Freyer, J . I \ , Wilder, M . E . , and Raju, M . R.: Rapid assay for cell age response to radiation by electronic volume flow cell sorting . . . . . . . 91
Friedberg, W. , Faulkner, D . N . , Neas, B . R., Hanneman, G . D . , Darden Jr, E . B . , Deal Jr, R. B . , and Parker, D . E . : Dose-incidence relationships for exencephalia, anophthalmia and prenatal mortality in mouse embryos irradiated with fission neutrons or 250 k V X-rays . . . . . . . . . . . 223
Friends of the Earth: Letter to the Editor 499 Fritsch, P., Beauvallet, M . , Jouniaux, B. , Moutairou, K . , Metivier, H . , and Masse, R.:
Effects of the chemical forms and valency states of neptunium on its jejunal transfer in the rat . . . . . . . . . . . . . 505
Fritsch, P., Beauvallet, M . , Moutairou, K , Metivier, H . , and Masse, R.: Acute lesions induced by a-irradiation of intestine after plutonium gavage of neonatal rats . 1
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enzymes by characteristic X-rays: analysis of the data of Jawad and Watt . . 651 Goodhead, D . T . , see Roberts, C . J . Goud , S. N . , Feola, J . M . , and Maruyama, Y . : Sperm shape abnormalities in mice
exposed to Californium-252 radiation. . . . . . . . . 755 Grdina, D . J . , see Hanson, W . R. Green, M . H . L . , and Lowe, J . E . : Failure to detect a D N A repair-related defect in the
transfection of ataxia-telangiectasia cells by enzymatically restricted plasmid . 437 Gr iem, M . L . Book review . 343
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Grinfeld, S., Gilles, J . , Jacquet, P. , and Baugnet-Mahieu, L . : Late division kinetics in relation to modification of protein synthesis in mouse eggs blocked in the G 2 phase after X-irradiation 77
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Haipek, C . A . , see Mitchel l , D . L . Hanneman, G . D . , see Friedberg, W . Hanson, W . R., and Grdina, D . J . : Radiation-induced D N A single-strand breaks in
the intestinal mucosal cells of mice treated with the radioprotectors WR-2721 or 16-16 dimethyl Prostaglandin E 2 . . . . . . . . . 67
Harbich, R., see Frankenberg-Schwager, M . Harms-Ringdahl, M . , Anderstam, B . , and Vaca, C. : Heat-induced changes in the
incorporation of [H3]acetate in membrane lipids . . . . 315 Harms-Ringdahl, M . , Skog, S., and Tribukait , B. : Membrane fatty acid composition
and radiation response of Bp8 sarcoma ascites tumor cells . . . . . 615 Hartmann, H . , see Schuessler, H . Haustein, K . , see Schneeweiss, F . H . A . Hempel, K . , and Mildenberger, E . : Determination of G-values for single and double
Strand break induction in plasmid D N A using agarose gel electrophoresis and a curve-fitting procedure . . . . . . . . . . 1 2 5
Hendry, J . H . : Book reviews 344,820 Henk, J . M . , see Freedman, L . S. Herskind, C. : Single-strand breaks can lead to complex configurations of plasmid
D N A i n v i t r o 565 Hieber, L . , Ponsel, G . , Roos, H . , Fenn, S., Fromke, E . , and Kellerer, A . M . : Absence
of a dose rate effect in the transformation of C 3 H 10T1/2 cells by a-particles . 859 Hodgkiss, R. J . , Roberts, I. J . , Watts, M . E . , and Woodcock, M . : Rapid-mixing of
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of ultrasound on cell kil l ing induced by ionizing radiation 627 Konings, A . W . T . , see Ruifrok, A . C . C . Kostial, K , Kargacin, B . , and Landeka, M . : Oral Z n - D T P A therapy for reducing
1 4 l C e retention in suckling rats . . . . . . . . . . 501 Kypenova, H . , see Svoboda, V .
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acids 253 M i , F. , see Shibamoto, Y . Michael, B . D . , see Prise, K . M . Michel , C . , see Balla, I. Mildenberger, E . , see Hempel, K . Mil ler , K , see Steeves, R. A . Mitchell , D . L . , Haipek, C . A . , and Clarkson, J . M . : Xeroderma pigmentosum variant
cells are not defective in the repair of (6-4) p h o t o p r o d u c t s . . . . . 201 Mönig, J . , Asmus, K - D . , Forni , L . G . , and Wil lson, R. L . : On the reaction of
molecular oxygen with thiyl radicals: a re-examination . . . . . 589 Mönig, H . , see Prütz , W . A . Moore, J . S., see Abelidis, S. Moore, J . S., see Metwally, M . M . K . More, C. , see Dardalhon, M . Moreno, G . , Atlante, A . , Salet, C. , Santus, R. , and Vinzens, F . : Photosensitivity of
D N A replication and respiration to haematoporphyrin derivative (Photofrin II) in mammalian C V - 1 cells . . . . . . . . . . . 213
Morse, M . L . , and Smith, D . S . : Cold-shock modification of the oxygen enhancement ratio of E s c h e r i c h i a c o l i cells . . . . . . . . . . 1 7 1
988 I n d e x of a u t h o r s ( w i t h t i t l e s )
PAGE
Moutairou, K . , see Fritsch, P. Moutairou, K , see Fritsch, P. Mühlensiepen, H . , see Feinendegen, L . E . Mulcahy, R. T \ , G ipp , J . J . , and Tanner, M . A . : Enhancement of misonidazole
chemopotentiation by mi ld hyperthermia (41 °C) i n v i t r o and selective enhancement i n v i v o . . . . . . . . . . . . . 57
Neas, B . R., see Friedberg, W . Nenot, J . C . Book review . . . . . . . . . . . 177 Nikjoo, H . , see Goodhead, D . T . Nishimoto, S., see Shibamoto, Y . Niwa, O., Saigusa, T . , Ikushima, T . , and Sugahara, T . : Activation of endogeneous
retroviruses in mouse cells by thermal neutrons . . . . . . . 949 Norman, A . , see Cameron Mitchel l , J . Nothelfer, R., see Ehrl ich, W .
O ' N e i l l , P. O., and Davies, S. E . : Pulse radiolytic study of the interaction of S 0 4 with deoxynucleosides. Possible implications for direct energy deposition . . . 577
O ' N e i l l , P. Book review 976 O ' N e i l l , P. O., see Austen, K . R. J . Okayasu, R., see Iliakis, G . Orr, J . Stewart Book review . . . . . . . . 1 7 7 Östling, O., and Johanson, K . J.: Bleomycin, in contrast to gamma irradiation,
induced extreme V a r i a t i o n of D N A Strand breakage from cell to cell . . 683
Pantelias, G . E . , see Iliakis, G . Parker, D . E . , see Friedberg, W . Peacock, J . H . , see Stephens, T . C . Penhaligon, M . , Courtenay, V . D . , and Camplejohn, R. S.: Tumour Bed Effect:
hypoxic fraction of tumours growing in preirradiated beds. . . . . 6 3 5 Plonka, A . : Letter to the Editor: Kinetics of hydroxyl radical induced poly(U) Strand
break formation in pulse-irradiated aqueous Solutions in the presence of oxygen 337 Pochin, E . E . : Meeting report: Health effects of low-dose ionising radiation—recent
advances and their implications . . . . . . . . . . 6 5 9 Ponsel, G . , see Hieber, L . Porciani, S., see Becciolini, A . Prise, K . M . , Davies, S.,<and Michael , B . D . : The relationship between radiation-
induced D N A double-strand breaks and cell k i l l in hamster V79 fibroblasts irradiated with 250kVp X-rays, 2-3 M e V neutrons or 2 3 8 P u a-particles . . 893
Prütz, W . A . , and Mönig, H . : Rapid communication: On the effect of oxygen or copper(II) in radiation-induced degradation of D N A in the presence of thiols . 677
Radford, L R . : Effect of cell-cycle position and dose on the kinetics of D N A double-strand breakage repair in X-irradiated Chinese hamster cells . . . . 555
Radford, I. R.: Use of 'nuclear monolayers' to identify factors influencing D N A double-strand breakage by X-rays . . . . . . . . . 8 5 3
Raju, M . R., see Freyer, J . P. Ravary, V . , see Dardalhon, M . Roberts, C . J . , and Goodhead, D . T . : The effect of 2 3 8 P u a-particles on the mouse
fibroblast C E I I line C 3 H 10T1/2 : characterization of source and R B E for cell survival . . . . . . . . . . . . . . 8 7 1
Roberts, I. J . , see Hodgkiss, R. J . Robins, H . I., see Steeves, R. A . Roman, V . , see Fatome, M . Roman, V . , see Vachon, A . Roos, II., see Ilieber, L .
I n d e x of a n t h o r s ( z v i t h t i t l e s ) 989
PAGK
Rosen, A . , Taylor, D . M . , and Darai, G . : Influencing of ionizing radiation on herpes simplex virus and its genome . . . . . . . . . . 795
Rosi, A . , see Bonincontro, A . Rowley, R.: Comment on the paper by Grinfeld et a l . . . . . . . 87 Ruifrok, A . C . C , and Konings, A . W . T . : Effects of amiloride on hyperthermic cell
ki l l ing of normal and thermotolerant mouse fibroblast L M cells . . . 385 Rustichelli, F . , see Albertini , G .
Saali, K . , see Juutilainen, J . Saigusa, T . , see Niwa, O. Salet, C . , see Moreno, G . Santus, R., see Moreno, G . Saran, M . , see Erben-Russ, M . Sasai, F . , see Shibamoto, Y . Satoh, S., see Eguchi, K . Sawada, S., see Ban, S. Schlappack, O. K . , Delic, J . I., Bush, C. , Stanley, J . A . , and Steel, G . G . : The
response of murine stem spermatogonia to radiation combined with 3-aminobenzamide. . . . . . . . . . . . . 7
Schneeweiss, F . H . A . , Tisl jar-Lentulin, G . , Haustein, K . , and Feinendegen, L . E . : Letter to the Editor: Ter iodicar pattern of kinetics of D N A Strand break repair following y-irradiation of human T l -ce l l s . . . . . . . . 491
Schuessler, H . , and Hartmann, H . : The effect of a protein on the radiolysis of D N A studied by H P L C and pulse radiolysis . . . . . . . . 269
Schuler, F . , Csovcsics, C. , and Taylor, D . M . : Differences in the uptake of transferrin bound 2 3 9 P u and 5 9 F e into multicellular spheroids of hepatocytes form adult male rats . 883
Schull , W . J . Book review 497 Seaner, R., see Iliakis, G . Sedlak, A . , see Svoboda, V . Seidel, A . , see Hotz, G . Shecterle, L . , see Steeves, R. A . Shibamoto, Y . , Nishimoto, S., M i , F . , Sasai, K . , Kagiya, T . , and Abe, M . : Evaluation
of various types of new hypoxic cell sensitizers using the E M T 6 single ce l l -spheroid-solid tumour System . . . . . . . . . . 347
Siegel, F . L . , see Yatvin, M . B . Skog, S., see Harms-Ringdahl, M . Skov, K . A . , and Farrell, N . P.: Binding mode of 2-amino-5-nitrothiazole ( A N T ) in
platinum complexes, t r ans - [P tC l 2 (ANT) 2 ] , affects D N A binding, toxicity and radiosensitizing ability . . . . . . . . . . . 289
Skov, K . A . , see Chan, P. K . L . Smith, D . S., see Morse, M . L . Smith, H . : Statement from the 1987 Como meeting of the International Commission
on Radiological Protection 969 Sportelli, L . , see Bonincontro, C . Stanley, J . A . , see Schlappack, O. K . Steel, G . G . , see Schlappack, O. K . Steel, G . G . , see Stephens, T . C . Steeves, R. A . , Robins, H . I., Mi l l e r , K . , Mar t in , P., Shecterle, L . , and Dennis, W . :
Interaction of whole-body hyperthermia and irradiation in the treatment of A K R mouse leukemia 935
Stephens, T . C , Eady, J . J . , Peacock, J . H . , and Steel, G . G . : Split-dose and low dose-rate recovery in four experimental tumour Systems . . . . . . 1 5 7
Stratford, I. J . , see Walling, J . M .
990 I n d e x of a u t h o r s ( w i t h t i t l e s )
PAGE
Stratford, M . R. L . , see Watts, M . E . Sugahara, T . , see Niwa , O. Surdhar, P. S., and Armstrong, D . A . : Reduction of substituted flavins by CO~ 2 and
cyclic disulphide anions . . . . . . . . . . . 4 1 9 Svoboda, V . , Sedlak, A . , Kypenova, H . , and Budenikova, D . : Long-term effects of
low-level 2 3 9 P u contamination on murine bone-marrow stem cells and their progeny . . . . . . . . . . . . . . 5 1 7
Takakura, K . , Ishikawa, M . , and Ito, T . : Action spectrum for the induction of single-strand breaks in D N A in buffered aqueous Solution in the wavelength ränge from 150 to 272 nm: dual mechanism . . . . . . . . . . 667
Takeda, H . , and Iwakura, T . : Evaluation of radiation dose resulting from the ingestion of [ 3 H ] - and [ 1 4 C]thymidine in the rat 957
Tanner, M . A . , see Mulcahy, R. T . Taylor, D . M . , see Rosen, A . Taylor D . M . , see Schuler, F . Taylor, J . M . G . , Withers, H . R., Vegesna, V . , and Mason, K . : Fitt ing the linear-
quadratic model using time of occurrence as the end-point for quantal response multifraction experiments . . . . . . . . . . 4 5 9
Thames, H . D . , see Travis, E . L . Tisl jar-Lentulin, G . , see Schneeweiss, F . H . A . Travis, E . L . , Thames, H . D . , Watkins, T . L . , and Kiss , I.: The kinetics of repair in
mouse lung after fractionated irradiation 903 Tribukait , B . , see Harms-Ringdahl, M . Twentyman, P.: Meeting report: T h i r d International Conference on Spheroids in
Cancer Research. . . 811
Vaca, C , see Harms-Ringdahl, M . Vachon, A . , Roman, V . , Lecomte, C , Folcher, G . , Fatome, M . , Braquet, P., and
Berleur, F . : A radioprotector: cysteamine, inhibits oxygen transport in lipidic membranes 847
Van der Merwe, K . J . , see van Rensburg, E . J . Van Rensburg, E . J . , Louw, W . K . A . , Van der Merwe, K . J . : Changes in D N A
supercoiling during repair of gamma-radiation-induced damage. . . . 693 Vegesna, V . , see Taylor, J . M . G . Vinzens, F . , see Moreno, G . Visscher, K . J . , de Haas, M . P., Loman, H . , Vojnovic, B . , and Warman, J . M . : Fast
protonation of adenosine and of its radical anion formed by hydrated electron attack; a nanosecond optical and dc-conductivity pulse radiolysis study . . 745
V i t i , V . , see Albert ini , G . Vojnovic, B . , see Visscher, K . J .
Walling, J . M . , Stratford, I. J . , and Adams, G . E . : Radiosensitization by the 2,4-dinitro-5-aziridinyl benzamide C B 1954: a structure/activity study . . 31
Warman, J . M . , see Visscher, K . J . Warters, R. L . , Brizgys, L . M . , and Lyons, B . W . : Alterations in the nuclear matrix
protein mass correlate with heat-induced inhibition of D N A single-strand-break repair 299
Watkins, T . L . , see Travis, E . L . Watt, D . E . , and Yonnis, A . - R . S.: Letter to the Editor: Physical mechanism for
inactivation of metallo-enzymes: Response to correspondence from Goodhead and Nikjoo 657
Watts, M . E . , Dennis, M . F . , Jones, N . R. , and Stratford, M . R. L . : A comparison of the intracellular uptake and radiosensitization efficiency in different media of uncharged 2-nitroimidazoles of varying lipophilicity . . . . . 359
Watts, M . E . , see Hodgkiss, R. J . Wielckens, K . , see Dikomey, E .
I n d e x of a u t h o r s ( i v i t h t i t l e s ) 991
PAGE
Wilder, M . F. , see Freyer, J. P. Wil lson, R. L . , see Mönig, J . Withers, H . R., see Taylor, J . M . G . Woodcock, M . , see Hodgkiss, R. J.
Yaguchi, M . , see Eguchi, K . Yatvin, M . B . , Clark, A . W. , and Siegel, F . L . : M a j o r i , coliheat-stress proteinsdonot
translocate: implications for cell survival . . . . . . . . 603 Yonnis, A . - R . S., see Watt, D . E .
IXT. J. RADTAT. RIOL., 1987, VOL. 52, NO. 6, 993-998
S U B J E C T I N D E X
P A G Ii
Abstracts ( A R R / B I R meeting) Abstracts (Netherlands Radiobiological Society) Adenosine and its radial anion Adenosine protonation . . . . . Adenosine radial anion protonation. Agarose electro-phoresis A K R mouse leukemia . . . . . Alcohol dehydrogenase . . . . . Alpha irradiation. . . . . . Amiloride . . . . . . . 3-aminobenzamide . . . . . . Anopthalmia . . . . . . . Antidoxidants . . . . . . . A R R / B I R meeting (Abstracts) Ataxia-telangiectasia . . . . . Auger electrons . . . . . .
Bacteria, sensitisation 921 Biochemical indicators of tissue injury 767 B I R / A R R meeting (Abstracts) 481 Bleomycin, D N A damage . 683 Bone marrow cells, thymidine kinase 469 Buthionine sulphoximine . . . . . . . . . . . 735
Dispersive kinetics, poly(U) Strand breaks Dithiothreitol radical Diurnal effects, polyamines in spieen D N A damage by auger emitters D N A double-strand breaks D N A effects ( A R R / B I R abstracts) . D N A Polymerase ß, hyperthermia . D N A radiation inactivation D N A radiolysis, protein effect. D N A repair D N A repair cell cycle D N A replication, photosensitivity . D N A single-strand breaks . D N A Strand breaks, periodical pattern D N A transfection . . . . DNA-pro te in crosslinking DNA-unvvinding technique Dose assessment, biological indicators Dose-rate effect, tumours D T P A , 1 4 1 C e retention .
E . c o l i . . . . . Electronic volume cell sorting Embryonic development Embryotoxicity E M T 6 cells . Enzyme demetallization Erythrocyte membranes E S R spin labelling . Exencephalia . Experimental mouse tumours Experimental tumour Systems
171, 603, 921 91
787 371 347 413 447 847 223 191 157
Far U V radiation 5 9 F e , hepatocyte spheroid uptake Flavin radicals. Flavones . . . . . Formate radicals Fractionation, tumours and lung Free radicals, fatty acids . Friends of the Ea r th / ICRP letter
667 883 419 393 419
157, 903 253 499
G-values . Glutathione.
125 43, 185, 853
Subject i n d e x 995
Haematoporphyrin derivative Haemoglobin, membranes Haemopoietic C F U - S Heat stress proteins. Hepatocyte spheroids Hepatocytes Herpes simplex virus Homeoviscous adaptation H P L C , D N A radiolysis . Human organ Systems, sensitivity Human fibroblasts, glutathione Hyperthermia . Hypoxie cell sensitizer Hypoxie fraction Hypoxie toxicity, platinum
I C R P . . . . Indirect action. Infectivity of viral D N A . Intestinal absorption Intratumoural dosimetry. Iodine-125 1 2 5 iododeoxyuridine
Late effects Late responding tissue Leukemia Linear quadratic model . Linoleic acid peroxyl radicals L i p i d biosynthesis L i p i d peroxidation Lipophil ic i ty . Liposomes Logistic regression L o w dose rate . L o w energy X-rays Low-dose ionizing radiation Lung . . . . Lymphocyte subpopulations Lysosomes
Magnetic fields . . . . Mechanisms of sensitisation Meeting reports Melanoma, D N A lesions. Membrane fatty acid composition Membrane lipids M e m b r a n e s . . . . . Metal uptake, spheroids . Metallo-enzymes, inactivation. Methionine dipeptides Microspheres, WR2721 . Microwaves . . . . Mi l i ta ry radiobiology (book review) Misonidazole . . . . Mouse eggs, G 2 block Mouse fibroblasts, amiloride effects.
PAGE 213 447 517 603 883 723 795 315 269 820
43 57, 299, 315, 385, 775
347 635 289
499,969 651,657
795 505 191 705 517
459 903 935 459 393 315 253 359 145 459 859
651,657 659 903 693 723
469,787 921
659, 811, 814, 969 115 615 615
315, 447, 603 883
651, 657 139
21 325 344
57, 281, 965 77
385
996 Subject i n d e x
PAGÜ
Mul t ip le chromosome breaks, mechanism . . . . . . . . 805 Mutant cell line, restriction enzymes . . . . . . . . 5 3 7 Mutat ion, Californian 252 245
Radiosensitization . . . . Radiosensitizer, platinum Radiosensitizers, 2-nitroimidazoles . Rapid-mix, sensitisation . Rate constants, thiyl radicals . Relative biological effectiveness ( R B E ) Repair, nuclear matrix protein Repair kinetics, Strand breaks and lung Repair of potentially lethal damage . Respiration, photosensitivity . Restriction endonuclease, chromosome breaks. R N A and D N A synthesis, thiopyronine photosenzitisation R S U 1069, rapid mix Ruthenium, complexes .
Sarcoma ascites tumour cells S C E sensitizers Seeds . . . . Single-strand D N A breaks Skin, radiation damage . Soft X-rays Sperm shape abnormalities Spermatogonia Spermidine Spermine. Spheroids . . . . Spleen . . . . Split dose effects Storage effect in seeds. Strand breakage in poly (U) . Structural modification in liposomes Structure/activity relationship, sensitizers Substituted flavins . . . . Suckling rats, 1 4 1 C e retention . Sulphate radical anion Supercoiling of D N A
Tl -ce l l s , D N A repair . Targetting, platinum Temperature effects on seed sensitivity Testis, spermatogonical sensitivity . Testis weight, Californium 252 6 - T G r , Californium 252 . Thermal effects of microwaves Thermal neutrons, viruses Thermosensitization Thermotolerance. . . . . Thiol-depleted mammalian cells Thiols , D N A breaks Thiopyronine, photodynamic effects T h i y l radicals, oxygen effect . Three-electron bond, methionine dipeptides 1 4 C-thymidine , dosimetry after ingestion 3 H thymidine, dosimetry after ingestion . Thymidine kinase, magnetic fields . Total body irradiation (TBI ) , leukaemia . Transferrin, spheroids . . . .
PAG F.
281, 677 289 359 281 589
237, 245, 871 299
491, 903 705 213 537 207 281
49
615 481 827 667 481 805 755
7, 237 767 767
347, 811, 883 767 761 827 337 145
31 419 501 577 693
491 289 827
7, 237 755 245 325 949 775
385, 775 735 853 207 589 139 957 957 469 935 883
315,
998 S n b j e c t i n d e x
Transformation, proton induced Translocation, heat stress protein . Tumour bed effect . . . .
U . V . damage . . . . . Ultrasound . . . . .
Vacuum U V radiation, D N A breaks Valency states, neptunium Vasculature ( B I R / A R R abstracts) . Vindesine, prenatal development Virus induction, thermal neutrons .
Water content of seeds . Whole body hyperthermia ( W B H ) . WR-2721
X-rays and vindesine, prenatal development Xeroderma pigmentosum
