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EXPERIMENTAL TREATMENT OF TUMORS IN MICE Floyd C. Turner, M. D. Laboratory for Research on the Treatment of Cancer Box 807, Boulder Creek, California This list includes substances tested since this program began, in 1936, at the Harvard Medical School. It was continued at the National Cancer Institute and is now being carried on in my own Laboratory for Research on the Treatment of Cancer, Box 807, Boulder Creek, California. Materials and Methods The experimental animals were inbred strains of mice. The C3H, BALB/c and the DBA/2 strains, bred in this laboratory, have been named the Tu (Turner) strains by the International Commission for Zoological Nomenclature. A preliminary study of the nature of each material to be tested was made and one or more preliminary experiments were performed in non- cancerous mice (these preliminary experiments are not recorded here) in or der to determine toxicological and pharmacological properties and to deter mine dosages for mice. For therapy, full tolerance doses were administered. This amount varied with differing substances because of differences of rapid ity of assimilation and elimination, cumulative and other effects. The doses were administered daily, usually by intraperitoneal injection, from the start of the experiment, continuously to the death of the last surviving cancerous mouse. Variations from this procedure are recorded in the tabulation. Treat ments were started when the transplanted tumors were about ten millimeters in their greatest diameters. Inasmuch as spontaneous cancers do not occur in 543 Research. on December 29, 2020. © 1958 American Association for Cancer cancerres.aacrjournals.org Downloaded from
Transcript
Page 1: EXPERIMENTAL TREATMENT OF TUMORS IN MICE...T-Tak Takamine Laboratories DST Dr. D. S. Tarbell JWT Dr. J. W. Thompson Tung Tung Oil Investigations - Department of Agriculture FCT Dr.

EXPERIMENTAL TREATMENT OF TUMORS IN MICE

Floyd C. Turner, M. D.Laboratory for Research on the Treatment of Cancer

Box 807, Boulder Creek, California

This list includes substances tested since this program began, in

1936, at the Harvard Medical School. It was continued at the National Cancer

Institute and is now being carried on in my own Laboratory for Research on

the Treatment of Cancer, Box 807, Boulder Creek, California.

Materials and Methods

The experimental animals were inbred strains of mice.

The C3H, BALB/c and the DBA/2 strains, bred in this laboratory,

have been named the Tu (Turner) strains by the International Commission for

Zoological Nomenclature.

A preliminary study of the nature of each material to be tested was

made and one or more preliminary experiments were performed in non-

cancerous mice (these preliminary experiments are not recorded here) in or

der to determine toxicological and pharmacological properties and to deter

mine dosages for mice. For therapy, full tolerance doses were administered.

This amount varied with differing substances because of differences of rapid

ity of assimilation and elimination, cumulative and other effects. The doses

were administered daily, usually by intraperitoneal injection, from the start

of the experiment, continuously to the death of the last surviving cancerous

mouse. Variations from this procedure are recorded in the tabulation. Treat

ments were started when the transplanted tumors were about ten millimeters

in their greatest diameters. Inasmuch as spontaneous cancers do not occur in

543

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544 CancerResearch Turner

crops, they had to be used in differing sizes. Weekly measurements, in milli

meters, of the greatest diameters of the tumors, together with a rough outline

drawing of each tumor, were recorded. This gives a visual record of the suc

cessive sizes of every tumor which has been treated. Mice in which the tu

mors regressed were kept for the remainders of their lifetimes to ascertain

whether the tumors recurred. Necropsies were performed on all experiment

al mice. Pathological specimens were examined, but the desired criterion

was the total and permanent disappearance of the tumors leaving fairly healthy

mice. Untreated controls of mice with tumors were set up for groups of sub

stances, but, if a test showed suspected tumor damaging effects, repeat tests

were performed (and in the final tests) an untreated control mouse was set up

for every experimental mouse. Treated controls were used for vehicles, dilu

ents and in which more than one substance was tested in a given experiment.

Evaluation of Results

A "growth ratio" is used as a means of comparison of the rates of

growth of treated cancers to the rates of growth of the untreated control can

cers. This growth ratio is obtained by dividing (or by multiplying if the tu

mors became smaller during treatment) the average days treated by the aver

age growth of the tumors, in millimeters. Similarly, a growth ratio can be

obtained for the untreated control cancers.

I am indebted to the following-named persons and companies who

supplied the materials tested.

A-HA Dr. Homer Adkins

AA Agfa Ansco Corp.Abb Abbott Co.AC Arlington Chemical Co.

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Turner CancerChemotherapyScreeningData 545

ACC Anademin Chemical Co.

Agri U. S. Department of Agriculture

ACP American Chemical Paint Co.

ACy American Cyanamid Co.

AK American Kitchen Products Co.

CA Dr. Charles Armstrong

B-Bab B. T. Babbitt Inc.

CTB Dr. Carl Tabb BannerBAC Baker-Adamson Chemical Co.

JTB J. T. Baker Co.

Bov. Bovinine Co.BHK Braun-Knecht-Heimann Co.

C-CSCC California Spray Chemical Corporation

CBCC Chemical-Biologica 1 Coordination Center

Ciba Ciba Pharmaceutical Products Co.

BC Dr. Bert Christensen

CPR Corn Products Refining Co.

C+B Coleman and Bell

D-DC Delta Chemical Works

LD Lambi Demetre

Dif Difco Co.

E-EK Eastman Kodak Co.

EA Eimer and Amend Co.Endo Endo Products

EL Eaton Laboratories

F-Feed Feed store

FB Fritzsche Brothers

FW W. Frankel

G-Gal Dr. Emory Gal

G+G Drs. David Greenberg and Emory Gal

GBI General Biochemicals Inc.Gero Gero Products Inc.

Good Goodrich Chemical Co.

BFG B. F. Goodrich Chemical Co.

DG Dr. David Greenberg

JG Dr. Jesse Greenstein

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546 CancerResearch Turner

H-PH Dr. Paul Henshaw

HWD Hynson-Wescott and Dunning

JH Dr. John Hartwell

LH Dr. Leslie Hellerman

CMH Chas. M. Higgins and Co.HR Hoff man-LaRoche

I- IMC International Minerals Chemical Corp.

J-JC Julliard Cocroft Co.

K-HK Dr. Herbert Kahler

L-JBL Dr. J. B. Lackey

Led Lederle Co.JL Dr. Joseph LeiterELC Eli Lilly Co.SL Dr. Steele LivingstonLu Luther Ink and Stamp Pad Co.

M-Ma Mallincrodt Co.

Mass Massachusetts Antitoxin and Vaccine LaboratoryMath Matheson Co.MCB Matheson, Coleman and Bell Co.MM Dr. Mary MaverM Merck Co.

GBM Dr. George Burroughs MiderMRI Midwest Research Institute

EM Dr. Erich MosettigMCP Mutual Citrus Products Co.

N-NCI National Cancer Institute

NIH National Institutes of Health

NCR National Research Council

NRL Naval Research LaboratoryNap Napera Chemical Co.

O-O One Spot Co.

P-PD Parke, Davis Co.

Pe Peebles Chemical Co.Per The Permuttit Co.

Phys Physicians Drug and Supply Co.

PG Procter and Gamble

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Turner Cancer ChemotherapyScreeningData 547

R-HR Dr. Henry Rapoport

RKR Dr. Roland K. RobinsRG Rockgas Co.SR Dr. Sanford RosenthalRo Rous Distributing Co.Rub U. S. Rubber Co.Ry Rystan Co.

S-Sand Sandos Chemical Works

AS A. Schilling and Co.CDS G. D. Searle Co.SR Sears, Roebuck and Co.See Seeman Bros, Inc.MJS Dr. Murray J. ShearSh Shell Development Co.She Shering Corp.MBS Dr. Michael B. ShimkinPJS Dr. Pendelton J. SlaughterLFS Dr. Lyndon F. SmallMIS Dr. M. I. SmithGFS G. F. Smith Co.SKF Smith, Kline and French Co.ERS E. R. Squibb Co.Sta Stanco Inc.SW Sterling-Winthrop Chemical Co.

AS Dr. A. StockSWI Superior Writing Inks Co.

T-Tak Takamine Laboratories

DST Dr. D. S. TarbellJWT Dr. J. W. ThompsonTung Tung Oil Investigations - Department of Agriculture

FCT Dr. Floyd C. Turner

V-VP Van Patten Pharmaceutical Co.

W-WHW Wm. H. Warner Co.

WCW Waterbury Chemical WorksWei Wellcome Research LaboratoriesWil Dr. W. H. WileyWin Winthrop Chemical Co.WRI Winthrop Research Institute

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548 CancerResearch Turner

Other Abbreviations

MCA MCA Sarcoma - the original tumor was induced by 20-Methyl-

cholanthrene in a DBA/2 mouse.HP Harding-Passey melanoma.

S 37 Sarcoma 37.Sp Spontaneous tumor.Tr Transplanted mammary adenocarcinoma.

The strains of mice used are denominated according to the recommendationsof the International Committee on Standardized Nomenclature for InbredStrains of Mice, Cancer Research, August 1952.

ale Alcoholaq. wateraq. dest distilled wateremul. The stock emulsion contained mineral oil, water, a psyllium

seed demulcent and 1/4% phenol for preservative.gly Glycerolprop Propylene glycolhorn. Homogenate - ingredients mechanicall suspended in water.

CMC Aqueous colloidal solution, usually 1/4%, of carboxymethyl-cellulose, a suspending agent for water-insoluble substances.

wet ag. Wetting agent.

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Turner CancerChemotherapyScreening Data 549

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550 CancerResearch Turner

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Turner CancerChe-motherapyScreening Data 551

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552 CancerResearch Turner

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Turner CancerChemotherapyScreening Data 553

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554 Cancer Research Turner

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Turner Cancer Chemotherapy Screening Data 555

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3IOofr-

COcoUWo

coDOUNJ^.^.-hydroxy-N-propyl

nehydrochlorideIIE

p¿i.~

°-COf-00cnrtmtí»\aitD

^t-

•¿�^COier«in

€¿�4oà

coaicoo*•oaS

j=-.-hydroxy-N-propy!

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t-«fTfSo01

coo1

30ß-XSCO0coo"i1i_1(s1o3I1

|oi3

1il4&

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Page 14: EXPERIMENTAL TREATMENT OF TUMORS IN MICE...T-Tak Takamine Laboratories DST Dr. D. S. Tarbell JWT Dr. J. W. Thompson Tung Tung Oil Investigations - Department of Agriculture FCT Dr.

556 CancerResearch Turner

co «

co m

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TOTALNO,

VEHICLEDOSESS

eOBOK0PflrtKW0

l.s

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uIMATERIAL

TESTED¡iUCOioÈ0"&.<;Boe^4O11§-Amino-7-hydroxy-l-u-triazolo-

pyrimidineIOCi*^ocoIOoAPScnoiniO"E

O3è-Amino-7-hydroxy-l-u-triazolo-

pyrimldineIOC«Ci^*IOts0fi^ODOffl1o^1

Nsp-Amlno-7-hydroxy-l-u-trIazolo-pyrimidineandTriethylene-s-tIOco21-10

Oi1g

s00fi«£»enS0)"H1él-Amino-7-hydroxy-l-u-trlazolo-

pyrlmldineandMethyl-bis-(chlethyD-aminc

hydrochlorldeIOI**CDCDyog

§oefi5«to0aS"g-Amino-7-hydroxy-l-u-triazolo-

pyrlmldineandColchicineu4gCi•"*002*ClO0A•ïVi0Mb3ig-Amino-7-hydroxy-l-u-triazolo-pyrimidineIOtem01H00

O00oo0OsT

riethyleneimino-s-triazine

Colchicineio^*aKj<I

\—m0B1§-Amino-7-hydroxy-l-u-triazolo-

pyrimklinu(0.5%HN03)ad.lib.IOt-l^5IO

(Mc-0

oO«S<

"\nno.ÕÕ"CI

sSsis-Amino-7-hydroxy-l-u-triazolo-

pyrimtdineandProteaseIO00o1-1IOIO3t-

eneo^00o,09•>00o«•8

s»g-iSè-Amino-7-hydroxy-

1-u-triazolo-

pyrimidineandProteaseIOAOí

Ci"-10co7IflIO

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sè-Amino-7-hydroxy-l-u-trìazolo-

pyrimidineandCathepslnIO0o0

N'-'co

t-D*rtCIoS•>BopB(HB11§-Amlno-7-hydroxy-l-u-triazolo-pyrimidineIO0o^-00

Ooo000OsTriethyleneimino-s-triazine

ColchicineIOco

coÈo

u><->0^UeQ0.Õ1

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-es?-Amino-7-hydroxy-l-u-triazolo-pyrimldineandAmmoniumchl<IOcio0

C4

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Page 15: EXPERIMENTAL TREATMENT OF TUMORS IN MICE...T-Tak Takamine Laboratories DST Dr. D. S. Tarbell JWT Dr. J. W. Thompson Tung Tung Oil Investigations - Department of Agriculture FCT Dr.

Turner CancerChemotherapyScreening Data SSI

^OtaUMGROWTH

RATIO?s,

IOüM*ÜO)

05a1«o°lì>

Jo< °e

S,

u<mssHJUS

ue»o

SiS3ftfiwy

t.SJ-1E2SOURCEMATERIAL

TESTED*„e*m

toSt«IOfIO

inOi-«

OOèÎcnok•BAmino-7-hydroxy-l-u-triazolo-(

pyrimidine,AmmoniumchlorideColcbicineiIOocor-

•¿�$IO1f!ÕΕBs1

ioe»EJ«0Lederle

JTBèAmino-7-hydroxy-l-u-triazolo-(

pyrimidine(0.25%HNOs)i«^t-OOMOO007inM

t-O

0oSSO0Lederle

TakieAmino-7-hydroxy-l-u-triazolo-(

pyrimidineandProteaseitoN

m-i-

IAt-(

IO«

r-«•¿�-<N

~4to

ot-•¿�*C4f

tg

«t0t^OO

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S1Q

<o

o1-1f-H01-

<*Ig5ieAmino-7-hydroxy-l-u-triazolo-(

pyrimidineandYeastAmino-2-methylnaphthol

hydro

chloridei

iw -^«fe-lO(0intu«0IO0&cou00Wfe»4Amino-2-methylnaphthol

hydro

chlorideiN<Di-iB^(0

HC4CD7IO

C4Ot-

CODOUik.C4m

EiAminomethylphenanthrene

hydro

chlorideiAIOint*o

coODCO«O

00frtOAcou40^miAminomethylphenanthrene

hydro

chlorideo>rrIOr-l§$CPss*Acou0404OfeS3O1•411i1inIOIOtoHIIOIO7onDOUq•3taa(2-

Amino-1-oxopropyl)-phenan-

threnehydrochloridei04„«000o

to2S3fIOo&coO00E(2-Amino-l-oxopropyl)-phenan-

threnehydrochlorideit-t-10«DSM5o-90IOa.ICO00iO•o1Amino-8-naphthol-2,4-dlsulfonic«-<-c-0«0N

C4HèoIO*Ag0300i"3•dsAmlno-8-naphthol-3,6-dlsulfonici«t-cn(0aCIcr

9oIO*o.

nicoOOFelton*oAmino-S-naphthol-4-sulfonic

aciIO•>KH(0toO)00

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Page 16: EXPERIMENTAL TREATMENT OF TUMORS IN MICE...T-Tak Takamine Laboratories DST Dr. D. S. Tarbell JWT Dr. J. W. Thompson Tung Tung Oil Investigations - Department of Agriculture FCT Dr.

558 CancerResearch Turner

t s* H nO <¿c; 2

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feS

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2îo4>USuC^00K.lË3-(2-Amino-l-oxopropyl)ph<

hydrochloride008oAE

O»HIGOt.19

K3-(2-Amino-1-oxopropyl)ph(

hydrochlorideCisOfm

ocn»04CJSi¡gì9-(2-Amino-l-oxopropyìphc

threnehydrochlorideSsd-

HO^U0PCo»04E¿9-(2-Amino-l-oxopropyl)-s-

phenanthrenehydrochloritCMCMcrrtIO0aWÅ“co

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(2-Amino-1-oxopropyl)-s- phenanthrenehydrochlori«CMCMto0IOco

CDOm^•-100^|

1I<iCM1CMJ

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toü

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a coto cocoffi

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chlorideSMIO£ïâ0CQ

0Ammonium

formate0C4t

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Sco

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Page 17: EXPERIMENTAL TREATMENT OF TUMORS IN MICE...T-Tak Takamine Laboratories DST Dr. D. S. Tarbell JWT Dr. J. W. Thompson Tung Tung Oil Investigations - Department of Agriculture FCT Dr.

Turner Cancer Chemotherapy Screening Data 559

coHBCOMSoÕS

fr* NCMCC

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co111¿C

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pH—

iCOCOtO"*»«^—j^l^fH^-l^^,-,^inC4tDNN^-.^i¿

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560 CancerResearch Turner

COH1ROWTH

RATIOUL*

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5S^>T3O>

|<cH«

uHSöZ

co¿

OT£°ulKuw

t*OETUMORiMU

t.SIguu¡aSMATERIAL

'li«COX.e»c-^co0

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eocoUacoiArachidic

acidtosMCOCOX

IOt-~goUcjinC4C.

COacCOU00ÃŽArachidic

acidtoIOoCMmCOIOt-3AU

0IOt-CO

COu<•*ie11N-Arachidic

acid(frt-ico<OXt-Smo<7Ì0COètCMUsça

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co04(N

00OXXX.

tous

in--<o

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trlsulfideArsenicpentoxide

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0^s ssCJN CM*2(DnC4fr»^1leer

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tricarboxyllci

saltM§04CO04xcnÌOciaCN»

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tricarboxylici

saltcoco0

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acidS§CO^X

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Sol.IOCO0

CNCOCOXfr»

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chlot-§IO

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Page 19: EXPERIMENTAL TREATMENT OF TUMORS IN MICE...T-Tak Takamine Laboratories DST Dr. D. S. Tarbell JWT Dr. J. W. Thompson Tung Tung Oil Investigations - Department of Agriculture FCT Dr.

Turner CancerChemotherapyScreening Data 561

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562 CancerResearch Turner

RESULTS

Av.DaysTumor

TOTALNO.TR.LivedGrovrth(mm)GROWTHEDOSESMICEControlsT/CRATIO«ICE

DOSE

>erStrainTUMORmgVEHICL^3WuBg

gEMATERIALTEOÕ

•¿�* IOCO•^

Oi COM\\\\CO

00 CDO•^

—¿�' t-cnlOtO IQP*«•-H

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a c. S «H co co AoSgu

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W W|iBenzyl

bromide

Benzylmalonicacid

Benzylisothloureahydr

BenzylmalonicacidCM

co <N co comm

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C*- t- t- OOp,-,-• -i Iß tu•¿�*iO

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Turner CancerChemotherapyScreening Data 563

o -eK eo

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TEST*t—

OSÄcooíTfuU3elQ,

OQ5en0i<UIM1C4*

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feo•o3M11

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30)iis-ldibromohvdroxybenzynMC4IO1t~000P,E.<£CQo"3l311i

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Page 22: EXPERIMENTAL TREATMENT OF TUMORS IN MICE...T-Tak Takamine Laboratories DST Dr. D. S. Tarbell JWT Dr. J. W. Thompson Tung Tung Oil Investigations - Department of Agriculture FCT Dr.

564 CancerResearch Turner

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mCOcr9IO0a

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mercaptalmCOMWca

to co «co<O

CO 04 CMTÕ«<*

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Page 33: EXPERIMENTAL TREATMENT OF TUMORS IN MICE...T-Tak Takamine Laboratories DST Dr. D. S. Tarbell JWT Dr. J. W. Thompson Tung Tung Oil Investigations - Department of Agriculture FCT Dr.

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Page 36: EXPERIMENTAL TREATMENT OF TUMORS IN MICE...T-Tak Takamine Laboratories DST Dr. D. S. Tarbell JWT Dr. J. W. Thompson Tung Tung Oil Investigations - Department of Agriculture FCT Dr.

578 CancerResearch Turner

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Turner CancerChemotherapyScreening Data 579

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580 CancerResearch Turner

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1958;18:543-606. Cancer Res   Floyd C. Turner  Experimental Treatment of Tumors in Mice

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