Pai
ntin
g an
alys
is o
f chr
omos
ome
aber
ratio
ns in
duce
d by
ene
rget
ic h
eavy
ions
in h
uman
cel
ls
Hon
glu
Wu,
Ph.
D.
NA
SA
Joh
nson
Spa
ce C
ente
r
https://ntrs.nasa.gov/search.jsp?R=20060053352 2018-06-20T00:04:39+00:00Z
S
GA
LAC
TIC
CO
SM
IC R
AD
IATI
ON
(GC
R)
(Pro
tons
to Ir
on N
ucle
i)
SO
UTH
ATL
AN
TIC
AN
OM
ALY
(Pro
tons
)
INN
ER
RA
DIA
TIO
N B
ELT
(Pro
tons
)
OU
TER
RA
DIA
TIO
N B
ELT
(Ele
ctro
ns)Th
e S
pace
Rad
iatio
nE
nviro
nmen
t
SO
LAR
PA
RTI
CLE
EV
EN
T(P
roto
ns to
Iron
Nuc
lei)
Rep
rese
ntat
ion
of th
e m
ajor
sou
rces
of i
oniz
ing
radi
atio
n of
impo
rtanc
eto
man
ned
mis
sion
s in
low
-Ear
th o
rbit.
Not
e th
e sp
atia
l dis
tribu
tion
ofth
e tra
pped
radi
atio
n be
lts.
NO
UTE
R R
AD
IATI
ON
BE
LT(E
lect
rons
)
Gal
acti
c co
smic
rad
iati
on
DS
B in
duct
ion
Low
-LE
TH
igh-
LET
Wu,
Dur
ante
, Geo
rge
and
Yan
g, R
adia
t. R
es.(
1997
)
Rad
iatio
n-in
duce
d ch
rom
osom
e ab
erra
tions
in ly
mph
ocyt
es in
vitr
o
Bio
dosi
met
ry re
sults
Sub
ject
TLD
read
ing
(cG
y)B
iolo
gica
l dos
e m
easu
red
usin
g va
lues
for
trans
loca
tion
(cS
v)
Ave
rage
RB
E*
13.
0616
4.2
23.
7818
3.8
35.
6820
2.8
44.
1623
4.4
54.
1614
2.7
64.
1612
2.3
*25%
cor
rect
ion
for h
igh-
LET
radi
atio
n in
TLD
mea
sure
men
t is
incl
uded
.
Mis
sion
dur
atio
n: 3
-5 m
onth
sA
ltitu
de: 1
90 N
MIn
clin
atio
n: 5
1.6
degr
ee
Why
do
we
stud
y ch
rom
osom
es?
Chr
omos
ome
aber
ratio
ns in
ast
rona
uts’
lym
phoc
ytes
are
ana
lyze
d to
de
term
ine
the
biol
ogic
al d
ose
rece
ived
from
long
-term
spa
ce m
issi
ons
Obj
ectiv
es
•Are
ther
e bi
o-si
gnat
ures
for s
pace
radi
atio
n ex
posu
re?
•Are
chr
omos
ome
aber
ratio
ns a
ssoc
iate
d w
ith ra
diat
ion
risks
?
Chr
omos
ome
stai
ning
/pai
ntin
g te
chni
ques
Gie
msa
FIS
H
mFI
SH
mB
AN
D
Chr
omos
ome
aber
ratio
n
Inte
r-ch
rom
osom
eex
chan
geIn
tra-c
hrom
osom
eex
chan
ge
Sta
ble
Uns
tabl
e
Telo
mer
e A
naly
sis
Wu,
Geo
rge
and
Yan
g, IJ
RB
(199
8, 1
999)
Mos
t of t
he in
com
plet
e ex
chan
ges
anal
yzed
with
FI
SH
are
act
ually
com
plet
e
Trul
y in
com
plet
e ex
chan
ges
in h
uman
lym
phoc
ytes
exp
osed
to
gam
ma
rays
in v
itro
0
0.1
0.2
0.3
0.4
0.1
110
100
1000
Unr
ejoi
ned/
Mis
rejo
ined
Inco
mpl
ete/
Com
plet
e
LET
(keV
/mic
ron)
Wu,
Dur
ante
, Fur
usaw
a, G
eorg
e, K
awat
aan
d C
ucin
otta
, Rad
. Res
. (20
03)
0
0.02
0.04
0.06
0.080.
1 0.1
110
100
1000
LET
(ke
V/m
icro
n)
Gam
ma
490
MeV
/uSi
500
MeV
/uFe
200
MeV
/u F
e•T
he fr
actio
n of
unr
ejoi
ned
chro
mos
ome
brea
ks a
re h
ighe
r for
hig
h LE
T
•Unr
ejoi
ned
brea
ks a
nd in
com
plet
e ch
rom
osom
al e
xcha
nges
are
pos
sibl
e bi
osig
natu
res
of h
igh-
LET
radi
atio
n
Hum
an fi
brob
last
cel
ls e
xpos
ed to
radi
atio
n of
diff
eren
t qua
litie
s
Hig
h-LE
T ra
diat
ion
indu
ces
mor
e un
rejo
ined
DN
A d
oubl
e st
rand
bre
aks
Des
ai, D
avis
, O’N
eill,
Dur
ante
, Cuc
inot
taan
d W
u, R
ad. R
es. 2
005
Si
Fe
Com
plex
abe
rrat
ions
--m
FIS
Han
alys
is
0
0.050.1
0.150.2
0.250.3
0.35
Com
plex
/Sim
ple
Exch
ange
sIn
com
plet
e/C
ompl
ete
Exch
ange
s
Ratio
6 G
y G
amm
a0.
7 G
y Fe
3 G
y Fe
Sim
ple
exch
ange
Com
plex
ex
chan
ge
Wu,
Dur
ante
, Fur
usaw
a, G
eorg
e, K
awat
aan
d C
ucin
otta
, Adv
. Spa
ce R
es. (
2002
)
0
0.050.1
0.150.2
0.250.3
Com
plex
/sim
ple
exch
ange
sIn
com
plet
e/co
mpl
ete
exch
ange
s
Ratio
Gam
ma
6 G
y
Fe io
ns 3
Gy
Fe io
ns 0
.7 G
ym
FIS
Hsh
owed
a h
ighe
r fra
ctio
n of
com
plex
and
in
com
plet
e ex
chan
ges
for
high
-LE
T
0
0.2
0.4
0.6
0.81
1.2
1.4
1.6
1.8
Gam
ma
6 G
yFe
ions
3 G
yFe
ions
0.7
Gy
2-w
ay e
xcha
nge
3-w
ay e
xcha
nge
4-w
ay e
xcha
nge
5-w
ay e
xcha
nge
6-w
ay e
xcha
nge
7-w
ay e
xcha
nge
8-w
ay e
xcha
nge
Com
plex
type
abe
rrat
ions
0
0.050.1
0.150.2
0.250.3
0.35
01
23
45
67
(b)
5 G
y ga
mm
aM
etap
hase
PC
C
Num
ber
of a
ber
rati
ons
Wu,
Geo
rge,
Kaw
ata,
Willi
ngha
m a
nd C
ucin
otta
, Rad
. Res
. 200
1
Inte
rpha
se v
s. m
etap
hase
: Iss
ues
of b
iosi
gnat
ure
(F ra
tio: R
atio
of d
icen
trics
to c
entri
c rin
gs)
Rad
iatio
nD
ose
(Gy)
Har
vest
m
etho
dF
ratio
γ ra
y2
PC
C15
.3±6
.3
γ ra
y2
Met
a12
.5±5
.9
γ ra
y5
PC
C8.
2±2.
0
γ ra
y5
Met
a9.
1±2.
5
1 G
eV/u
Fe3
PC
C5.
2±0.
9
1 G
eV/u
Fe3
Met
a9.
1±2.
2
Cen
trom
ere
prob
es w
ere
used
.
mB
AN
Dan
alys
is
Inte
r-vs
. int
ra c
hrom
osom
e ex
chan
ges
(mB
AN
D)
0
0.1
0.2
0.3
0.4
0.5
01
23
4
Intra
-exc
hang
eIn
ter-
exch
ange
01
23
4
137
Cs
γ-ra
y F
e (6
00 M
eV/n
)
Dos
e (G
y)
Aberrations in chromosome 3 / cell
Dos
e (G
y)
Fraction in damaged chromosome 3
0
0.2
0.4
0.6
Com
plex
exc
hang
eS
impl
e ex
chan
ge
2
4
0.2
5
0.5
1.0
1.5
2
.0
137C
s γ-
ray
Fe (6
00 M
eV/n
)
Fraction of total inversion
0
0.2
0.4
0.6
0.8
Inv+
Intra
+Int
erIn
v+In
ter
Inv+
Intra
Inv
137C
s γ-
rays
Fe
(600
MeV
/n)
mB
AN
Dan
alys
is
Mos
t inv
ersi
ons
wer
e in
volv
ed
with
oth
er in
ter-
and/
or in
tra-
chro
mos
ome
rear
rang
emen
ts
Ham
mon
d et
al.
Nat
ure
Med
icin
e 19
99
18+
18+
Do
spac
eflig
ht fa
ctor
s al
ter t
he c
ellu
lar r
espo
nse
to ra
diat
ion
expo
sure
?
Chr
omos
ome
aber
ratio
n fre
quen
cies
in p
re-a
nd p
ost-f
light
ast
rona
ut
lym
phoc
ytes
irra
diat
ed in
vitr
o w
ith lo
w-L
ET
radi
atio
n (W
u et
al.
Phy
s. M
ed. 2
001)
Nis
sion
: STS
-103
Dur
atio
n: 8
day
s
Bloo
d dr
aw s
ched
ule:
10
day
s be
fore
laun
ch, J
SC
, kep
t at 4
C fo
r 1 d
ay b
efor
e ex
posu
re0
days
afte
r lan
ding
, KS
C, k
ept a
t 4 C
and
rece
ived
ne
xt d
ay. K
ept a
t 4 C
bef
ore
expo
sure
14 d
ays
afte
r lan
ding
, KS
C, k
ept a
t 4 C
for 1
day
bef
ore
expo
sure
Irrad
iatio
n: W
hole
blo
od w
as ir
radi
ated
to g
amm
a ra
ys
Pro
cedu
re: W
hole
blo
od w
as s
timul
ated
to g
row
with
PH
A in
gro
wth
med
ium
an
d ch
rom
osom
es w
ere
colle
cted
follo
win
g st
anda
rd p
roce
dure
s.
Chr
omos
ome
anal
ysis
: Chr
omos
omes
#1
and
#5 w
ere
pain
ted.
Do
spac
eflig
ht fa
ctor
s al
ter t
he c
ellu
lar r
espo
nse
to ra
diat
ion
expo
sure
?
0
0.050.
1
0.150.
2
0.250.
3
00.
51
1.5
22.
53
3.5
STS-
103,
#59
R+1
4(48
h)
R+0
(60h
)
L-10
(48h
)
Dos
e (G
y)
Wu,
Geo
rge,
Willi
ngha
m a
nd C
ucin
otta
, P
hysi
caM
edic
a20
01
Gre
co e
t al.
Adv
. Spa
ce R
es. 2
003
Sum
mar
y
•FI
SH
, mFI
SH
, mB
AN
D, t
elom
ere
and
cent
rom
ere
prob
es h
ave
been
use
d to
stu
dy c
hrom
osom
e ab
erra
tions
indu
ced
in h
uman
ce
lls e
xpos
ed to
low
-and
hig
h-LE
T ra
diat
ion
in v
itro
•H
igh-
LET
indu
ced
dam
ages
are
mos
tly a
sin
gle
track
effe
ct
•U
nrej
oine
d ch
rom
osom
e br
eaks
(inc
ompl
ete
exch
ange
s) a
nd
com
plex
type
abe
rrat
ions
wer
e hi
gher
for h
igh-
LET
•B
iosi
gnat
ures
may
dep
end
on th
e m
etho
d th
e sa
mpl
es a
re
colle
cted
•R
ecen
t mB
AN
Dan
alys
is h
as re
veal
ed m
ore
info
rmat
ion
abou
t th
e na
ture
of i
ntra
-chr
omos
ome
exch
ange
s
•W
heth
er s
pace
flig
ht/m
icro
grav
ity a
ffect
s ra
diat
ion-
indu
ced
chro
mos
ome
aber
ratio
n fre
quen
cies
is s
till a
n op
en q
uest
ion.
Meg
umi H
ada
Fran
k C
ucin
otta
Dip
taB
andy
opad
hyay
Nira
vD
esai
Mar
co D
uran
teY
oshi
yaFu
rusa
wa
Ker
ry G
eorg
eTe
tsuy
a K
awat
aV
eron
ica
Will
ingh
am
