Biological Effects of Ionizing Radiation at Molecular And1
Transcript of Biological Effects of Ionizing Radiation at Molecular And1
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BIOLOGICAL EFFECTS OF IONIZING
RADIATION AT MOLECULAR AND
CELLULAR LEVELS
BIOLOGICAL EFFECTS OF IONIZING
RADIATION AT MOLECULAR AND
CELLULAR LEVELS
Module VIII-a
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Historical backgro!"
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Wilhelm Conrad Roentgen
Disco#$r% o& ' ra%s
()*+,-
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Disco#$r% o& ra!i./s !atral
ra"ioacti#it%
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First radiation-induced skin cancerreported
in 1902 First radiation-induced leukemiadescribed
in 1911
First r$0orts o! 1ar.&l
$&&$cts o& ra"iatio!
)+23s4 bone cancer a.o!g
ra"i. "ial 0ai!t$rs
)+53s4 liver cancer and leukemia"$ to T1rotrast a".i!istratio!
)+63s4 $7c$ss leukemia a.o!g
&irst ra"iologists
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St"i$s o& 8a0a!$s$
A9bo.b sr#i#ors
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E&&$cts o& ra"iatio! o! c$lls at
ato.ic l$#$l
Io!i:atio!E7citatio!
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M$c1a!a!is.s o& "a.ag$
at .ol$clar l$#$l
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Dir$ct actio!
Ionizing radiation + RH R-+ H+
OH IR C = NH
imidol (enol)
O IIR C = NH2
amide (ketol)
Tautomeric Shifts
Bond breaks
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e-X ray
rayP+
OH
HOH-
H+
Ho
OHo
I!"ir$ct actio!
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Ra"iol%sis o& H2O
.ol$cl$
Shared electron
Shared electron
H-O-H H++ OH- ioni!ation"
H-O-H H#+OH# $ree radical%"
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R$actio!s ;it1 &r$$ ra"icals
H3< OH3 HOH (r$co.bi!atio!-
H3 < H3 H2
("i.$r-
OH3
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E&&$cts o& o7%g$! o! &r$$
ra"ical &or.atio!
O7%g$! ca! .o"i&% t1$ r$actio! b%
$!abli!g cr$atio! o& ot1$r &r$$ ra"ical
s0$ci$s ;it1 gr$at$r stabilit% a!" lo!g$r
li&$ti.$s
H3
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Li&$ti.$s o& &r$$ ra"icals
&nm
Becau%e %hort li$e o$ %im'le $ree radical% (#-(#%ec") only tho%e $ormed in *ater column o$ -&nm around ,A are a.le to 'artici'ate inindirect e$$ect
Ho
OHo Ho
OHo
HOo RO
o
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R$latio! b$t;$$! LET a!"
actio! t%0$
Dir$ct actio! is 0r$"o.i!a!t ;it1
1ig1 LET ra"iatio!= $>g> al01a
0articl$s a!" !$tro!s
I!"ir$ct actio! is 0r$"o.i!a!t ;it1
lo; LET ra"iatio!= $>g> ' a!"
ga..a ra%s
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Bioc1$.ical r$actio!s
;it1 io!i:i!g ra"iatio!
DNAis 0ri.ar% targ$t&or c$ll "a.ag$ &ro. io!i:i!g ra"iatio!
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T%0$s o& ra"iatio! i!"c$"
l$sio!s i! DNA
Single-%trand .rea/% ,ou.le %trand .rea/%
Ba%e damage
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M$c1a!is.s o& DNA
r$0air
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DNA r$storatio! &ailr$
0nre1oined ,Adou.le %trand .rea/%
Incorrect re'air o$
,A damage
Cytoto2ic e$$ect Mutation%
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C1ro.oso.$s
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DNA l$sio!s a!"
c1ro.oso.$ ab$rratio!s
,A S3456
S7RA, BR6A8
,A ,O0B56
S7RA, BR6A8
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Ra"iatio! i!"c$"
c1ro.oso.al ab$rratio!s
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E&&$ct o& ra"iatio! o! c$ll
C$ll ki!$tics
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Ra"ios$!siti#it% o& c$ll
i! c$ll c%cl$
Relative
Survivability
4( S 4 4(MRelative survivability o !ells irradiated in dierent "#ases o t#e
!ell !y!le$ Syn!#ronised !ells in late %2and in mitosis (&) s#o'ed
reatest sensitivity to !ell killin$
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Mitotic "$at1
B$rgo!i@ a!" Tribo!"$as/
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The most radiosensitive cells are
acti#$l% 0roli&$rati!g?"i#i"i!g at t1$ti.$ o& $70osr$
!"i&&$r$!tiat$" (!o!9s0$ciali:$" i!
strctr$ a!" &!ctio!-
B$rgo!i@ a!" Tribo!"$as/
la;/ ()+3-
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I!t$r01as$ "$at1
1% ar$ 0$ri01$ral bloo" l%.01oc%t$s 1ig1l%
s$!siti#$ to ra"iatio!= alt1og1 ;$ll "i&&$r$!tiat$"
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Ra"iatio! i!"c$"
.$.bra!$ "a.ag$
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Dose rate and fractionation
Radiation quality
Temperature
Chemical modificationOxygen
Radiosensitizing agentsRadioprotectie agents
Mo"i&icatio! o& ra"iatio!
i!r%
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Dos$ rat$ a!"
&ractio!atio!
3
3>,
)
)>,
2
2>,
5
3
3>,
)
)>,
2
2>,
5
9rolonged e2'o%ure*ith lo*er do%e rate
Acutee2'o%ure*ith highdo%e rate
:ractionateddo%e
Acutedo%e
Ti.$Ti.$
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Ra"iatio! alit%
Survival curve for mammalian cells
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Survival curve for mammalian cells
exposed to
high- (A) and low-!T (") radiation
A
B
Dq
n
D0 D0
1-1/e1-1/e,037
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T$.0$ratr$
For c$ll kili!g $&&$cts= tiss$s ar$
.or$ ra"ios$!siti#$ at 1ig1$r
t$.0$ratr$s
C1ro.oso.$ ab$rratio!s i!cr$as$
at lo;$r t$.0$ratr$s (s00r$ssio!
o& r$0air 0roc$ss-
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C1$.ical .o"i&icatio!4
o7%g$!
OER Dos$ r$ir$" to cas$ $&&$ct ;it1 o7%g$!
Dos$ r$ir$" to cas$ $&&$ct ;it1ot o7%g$!
Dissol#$" o7%g$! i! tiss$s i!cr$as$s
stabilit% a!" to7icit% o& &r$$ ra"icals
O7%g$! $!1a!c$.$!t ratio (OER- is"$t$r.i!$" b%4
T1$ OER 1as a .a7i.. #al$ o& 5>3
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Ra"ios$!siti:i!g ag$!ts
Halog$!at$" a!" sbstitt$"
a!alog$s o& DNA bas$s4 ,9bro.o9
racil a!" 9t1io9ga!i!$
El$ctroa&&i!ic co.0o!"s4
Nitroi.i"a:ol$s (.iso!i"a:ol$=
!itroi.i"a:ol$= a!" !itro&ra!-s$!siti:atio! $!1a!c$.$!t ratio
(SER-o& )>2 to )>6
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Ra"io0rot$cti#$
ag$!tsT1iols(csteine! 2-"ercaptoet#la"ine!csta"ine and t#iourea$. %#iols #a&e dosereduction 'actor ()*F$ ratio o' 1.4 to 2.0
%#e are t#ou+#t to protect cells bsca#$!gi!g &r$$ ra"icals0ro"ci!g 1%0o7ia
t$.0oraril% i!1ibiti!g DNA s%!t1$sis= allo;i!gti.$ &or t1$ r$0air $!:%.$s to co.0l$t$ r$0airo& sbl$t1al "a.ag$
&or.i!g "isl01i"$ bo!"s i! 0rot$i!s= t1$r$b%
t t1 i t1