The influence of metabolic inhibitors on the response
of Chinese hamster cells to ultra- violet light
C. F. ARLETT
ff'cmlage Reseorch IA•boratory, A .E. R.E. , Want<tge, Berk&hire, Greot Britaitt
fntroduction.
Although there is a hody of cvid ence for the ability of Chinese hamster
cells (CHC) to repair hoth suh-lethal and potentially lethal damage inducccl
by ionizing radiation (ELKIND, WmntoRE & ALESCIO, 1964), there is ]imited
evidence for the repair uf lesiuns induced by ultra-violet light in this materia!.
At the hiochemical levcl, photoreactivating enzyme activity is ahsent
in ali rnammalian cells tested (CLEAVER, 1967; CooK & McGRATH, 1967)
a nd excision r epair has yet to be J emonstrated in cells of rodents (TaosKo,
CHu & CAIHUER, 1965; KLL\IEK, 1966). However, repair replication in Chinese hamster DNA has been reported hy CLEAVER (1968a).
At the lev~l of ecU survival the interaction experiments of ARLETT (1968)
using ultra-violet and gamma irradiation may be taken as indicating the
prcsence of repair processcs for UV damage in these cells. HAYNES (1964)
has shown that interaction is present where repair ability is a lso prescnt,
in E. coli B/r ancl diploid yeast , but ahsent where repair ability is also absent,
in E. coli B, and haploid yeast. When metabolic inhibitors were used in
an attempt to demonstrate thc prcsence of repair mechanisms no effects
werc observed in two clones of CHC (ARLETT, 1967). However, the prescnce
of a repair system sensitive to methylatcd xanthines but not acrifiavine
has bePn revealed in mouse L cells (RAUTR, 1967). This 1>uggests that there
may be a spccificitv of responsc of celi type to a particular inhibitor and,
in addition , the presence of rcpair can be inferred from a post-irradiation
effect evcn where thcre is ru) bioehemical evidence for processes presumed
to be involvcd in repair; mousn L cells do no t un d ertake repair replica ti o n
(CLEAVER. 1967).
T he prescnt communication providt~S ;;ome additional information on
the response of CHC t.o cbanges in the post-irradiation environment following
l'reatmcnt with ultra-violet !ight.
. t lln. I RI. SufJfr. Sanilir. ( lnr.!l)
5.
~11>7·375.
3flll
h\I.:TOR~ AFFJ..I.:TI Nl, l.:l.LLl LA Il I' JifiTO!--E'\ ~ 1\ JT\
Evidc•u c!' for tht· inhiiJ ilion of ri'JWÌr capacity Ly au~ <·ompolwd applit·d
a ~ a po;; t-irradiatiou trca tnwnt can lw acc~plt•tl nn l~- " lwrP it ha;, hcen ~olw,, n
tiJat thc· Lrc·atnwnt h as a s ignilicant r!l'cct willwut al tlw bamc· IÌnJt· n•ciLH·ing
thc• sun i H l l of contro! un irradia tt·d cells (\\1 u JTMORF &. TrLL. ] 964) .
Materia./.~ lutd
M etlwds.
D c tail ~ of thl' cultura! tecbniqnes us in~ a clom• F nf CH (' ( B E u~ OliO
& HALL, 1967) huH hPt'll puhlis h<·d c·lsc·whc·n· (Aau·:TT, 19hi). Thc· uul~­
si ~uifìeant changt·~' in rnu ti n<· cultura ! t echni1p w hav1• hePn th c• usc· of FJ O
IIIPclium a ud fol'lal ca lf Sl'rum frorn a t'utUmrrc ia l sourCt' (Fio" Luboraturit·'Ltd.). F.xpt•rimrn tt- wPre pcrformf'<l a~ drscrilwd earli1•r c•xct·pt lh at a 2 11 11
C02 Ìn air gas TnÌ X lUrt~ wa;. providc•cl in thc pJa lÌ t wo\\·th ltO X(>b ~~ ~ cl i:-SOJvi n g a \ 'ich y wat<•r tahll'l (British Oxygen Compan y) in wat!'r in tht• IHI X.
lu additiou th r Lime cou r~>~' of e>qwri m enl!:' ''a" chan~td ~o thal irradia lwn;,
w ere~ p crfèmued 2-3 h our~ <tftc·r pl ating, tlw cellula r multiplit•il r of thi ~
materia! wa ~ unii ~.
Tbc· H r La cells u sed in this iuHs tigation "<'T<' obtained fmm M.ILE.
J>orton antl grown on Eagl1•'t;. m cdi um w ith 10 1} 0 calf s1•rurn rnad .. al M. H.E.
Fur cxpPrÌm<'ntal purposrs tlwsc c<•ll;; Wf'rc ha ndlcd in tbe sanw wa~r as llw
CH C. thc period l w l wccn f>l atin~ a nel prrforrning ti w expcriuwnts !J f'i n ~
P>..tentlNI lo 6% hours and the me>dium b t·iu~ s upplcm ented wi1h a furt lwr
5 % fortal calf SCT IIIll.
n a ncl Du s un i"aJ para rn eters ancl tlu·ir standard (•rrors \\ C ff' calcula lc·d
u ing a program H rr kiutll) m aclt· H\ ailabll' h) Mr D. G. Pal"'orth. M.H .C.
Harwell fitting a ut u lli- taq~t· l s in glt hit modt·l. Tbe proportion of s uni viu~
cu looic·s wlwn thP clo!'l' of ratlia tion is D is a !loU III C'd tu lw : = s" ll - (l 11 11 11
- r
") 1 when · ~ 0 = pia t ing dll<·Ìc·n r). Dn =
do~c· whil'h rnluct•t- th t·
SUT\'Ì\·Ìng fraction hy 0.:17 01) tJw 1'Xp0lll'lltiaJ pari nf tJw I'Uf\ c· UHt l
n = e"'trapolation numher.
Thr data is p resPntr d frorn t lw results ohtain<'d u sing t'\\'(1 L r SUIIT('('~.
a 6W Philips TUV la mp givin g a Job <' to th t• surfacc· of thr cc>ll la~·r r of
9 ergs/mrn ~/~>PI' , u sing this lamp tlw n ·sults art• plottPd in ergi-. Tlw sernud
source was a Philip:. 30\1' TU\' lamp. the dusc· lwn· wa,.. 4 5 Prg.,/mm ~ SI'<',
1lw rrsult s obtained with th ~b lamp are plott1•d in scrnnds of cln:<t'.
Rt•sults.
Conlìrm.ntion of earlit•r ob.~;~·r vution.~.
Earli1·r r Psultt- b ave shown that methylatPd xanthines w<·n· wi thout
cfl'ect on CJI C foll owing irradia tion with UY (A HLErr, 1967) . ì'icga ti ve res ults
Rll <:h as tiH·Hc wert givtn g r<-atcr suh stance w hr n a sigu iGcant c·fl'c·c t. u sing
369
F ig . l. -
The inA ue nce of fì lt er s terilised caffe ine o n t b e s urvivu l of a sy nchronous
11 c La cclls, continuous pos t-irrnrliutiou t rea t me nts. T h e pl a ting d lì cir n cy of unirradiated Cl'lls in earh
m ediu m w as tuk en a s HJO per ceut
f.urvival whcn eomput.ing po in ts.
Lin es fit t ed by eye.
ron trol - u rvintl Il
1.95
O. ~l . Do - 1.97
O. IL
o--- o
*-----* 50 !Lg(ml caffeine, no toe - --e
Ol
l____L____i ___~----~--~~--~
x irity n = l. ll r 0.60,
Do
1.97
0.33
LOO fil!'ml caffeine, 20
per ct• nt o f con tro ) unirrad i at~d re lls killetl h y
the trf'a t men t , n - 0. .)9
11.19.
Ilo - 1.9 1
11.1 11
IO
Fi". 2.
IO
Th e in(Jtu' n ce of l'l h itliu m b rornitle
on t he "urvival nf aoyoch rouous
CHC to ultra-vio let J i~ ht. The plating efficicnr y of ttnirradiu trd «·r lls
in cnr h mcdiu m "ns taken ns 100
per cent survi' a l wh en c·otn puting
JWÌn ts. l.in es fi tted by eye.
\0
-
T op pa.nd.
pc rc«•n trJ~e Mtrv ivo l
nf u nirradiated cells in
tueclia rontatmug v nrio u8 c·oncen trut ions nf
r thi di um hromi de,
l
honr trealmt'n t o. The
rc•spon~c· fo llowin!! a p ritnin l{ dose of 2 'eco nds
,f ultra-\ iolt't light i~
alsn illu• trutrJ.
O - - -0 T hr
»~---------------------------;
Bottom pund.
0 - - - 0 <'on tro l snr vival
5.H
11
3.3, Do
1.79 - 0.22
~~ --- r.'r l hour pn,t-irrndiation
trcatmt'nt wit h l ;.L,: 'ml
!'thioli u m hrom id e no
toxi!'i t v. u
6.1
1.9,
IJo - :'?.06
O.ll
~ hu ur pust-irrud iat io n
t rcat nw u t -. i t h lO !.L!-(/ 1111,
no toxici t y. n
7.1
:!.Il. Do
1.80 c 0. 1 ~
~ hn ur post-i rradia t ion
tren t.m cnt with 50•.LJl: ml ,
:1() "., eon t rol. uui~radi.t­
ll•ol. c•t·ll~ ki lll'd lov th i~
*- --*
e- -- ·
oo L---~--~----L---~--~--~~
o
UY l.lPO$l.IIK
'"""'*' "
.,
t rra t rn r nt n -"
O..) l , Do
:!.08
luo.
1.«1. ,...,.,/Hl'. ;-.;,udtl (I!Jti!l)
n:79
0.3.)
5. :u;;.:J;,).
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37(1
t 'AG1'0R!- AFFE>X:1'JNG c •: LLULAR PIIOTO!>"NSIVITY
tbe sarnt' s ampl!· of cafl'e ine (Sigma Chemicals). was oLser ved following a p08 1·
irradiatiou treatmc·nt of asyncbronous H eLa celh, (Fi~. 1). IL is clear fiom
this results that an efi'cct can lw ol,tairwd in tht• ahseoce of any toxicity tu tllf•
ceUs aud that thesc HcLa cclls dn haw a repair system sousitiv<' l o cafl'riut·.
Compound.~
which birtd to nucleic acid.-..
Acriflavine aud actirwmycin D haYe ht>c•n sbown to be' without efl't·t~ l .
without also bcing toxic in CHC (AntET1', 1967). BotJr compounds ha vt
the propcrty of hioding to nudtir acids (G11'TELSON & W ALKER , 1967;
lliMILTON. FcLLEn & REICH. 1963) . Ont> other compound, ethidium bromidt·-2 , 7. diamino-phenyl phcnathridine 10 ethyl bromohydrull· (courtcs~
Boots CIH·micals) wab also exarninPd. The results obtairu·d for its efi'ect!i a~>llf'l' ~ll)lNI
100
-•-e,
..,
CY108 iN. AltUIH()51Df
HV()flt().V'LAMJNl
-·-i
i""
'a
1-- ·--.
' a
'
8~
•,
'!
."."
'-e
-
,
"s,
'" '
o
o,
ID
...
l
Fig. 3. -
...
.. .
.
The percentoge survival of o~yuchronous Cli C following irrodia t ioo with uhrn violel light. The ploting efficie nc) of unirrodiated cells in each medium was Lakr n
a~ 100 per cerll survival when computing poinlb. Lioes fitted b) eye.
Fir11 pane!.
0 - - -0 con tro! survivol, u = 4.9 ::!: 0.46, Uo = 76.5 :i 2.0
e---e
4 bour post-irruùiotiou treatmeut with 2000 fL~frnl th ymidinc, uo
toxicit y, n = 4.5 1- 0.40, Do = 79.0 ± 2.0
• econd pane/.
O - - -0 contro! su:rvival n
]3.3 _ 1.9, Uo
59.9 J 1.8
4 hour post-i rrodiotioo lreatment with 200 fLg/rrrl hydroxylnrninc,
30 per cc n t of con tro l unirradiotrd cells killc-d IJy treat meni,
u
7.9 ± 0.9. Do = 66.4 ± 2.0
e---•
=
Thirrl ptrnf'l.
:r 0.6. Do = 72.3 ± .1.9
4 hour post-irrodiotion treotment witb l fLgfml <'ytosinc arnbinoside, no t oxicity. n - 13.8 + 4.0, Do 57.2 l 3.8
0 - - - 0 co ntrol survival, n = 5.9
e---e
.An11. / si Super. Saniltl (19G9) 5 . 3G7·37S.
l
37l
ARLETI
a post irradia tion treatment of asynchronous populations of CHC are shown
in Fig. 2. This drug also binds to nucleic acids (WARI NG, 1966) has two
effects, it may increase survival, 4 hour treatments at l a nd lO {lg/ ml, or,
it may reduce !!Urvival, the treatment w ith 50 flg/ ml. Since the latter treatment r educes survival in cootrol unirradiatcd popula tions, the r esponse
hringing about an enbancement of survival is takcn as the effect of cthidium
bromide on this clone of CHC .
-
...,_.,_
CY fOI"M" AA~
."&~
l?~e
e""-.
·'0..
~
~e-~.
e"-. e
'
'
"'-
~~.
·~
e-e
·~
~~
u ~ • ---•
Fi ~t.
-t
Th e percentage survi val of synchronised cells of the Chioese hamster following
irradiotioo with ultra-violet light. Cells wer e in th e S p base of the cell c yr le
J hou.rs after the relcose of the s ynchronisiog thymidin e IJiock. The ploting eflìc iency of unirrodia ted cells in eorh medium was takeo os 100 per cen t survi va l
when computing points. Lines litted by e ye.
F i n11 pan~.
= 2.05 c 0.19
4 hour post-irrodiation treot ment with 2000 (Lg/m l thy midinc, no
toxicity n = 1.5 ± 0.6, Do - 2.13 : 0.19
0 - - -0 contro! survivo l, n = 1.8 ± 0.7 , Do
e
e
Second pan.el.
0 - - - 0 contro! survivul, n - 4.4 ± 0.6, Do = 2.01 :: 0.06
<. - - - .><. ~ hour post-irradiotion tr ea tment with 100 y.g/ m1 hydroxylam ioe,
:l.~
e
e
per 1·eot of contro! unirradiatcd cells kill ecl hy trcatmcnt,
n = 1.7 :: 0.2. Do = 2.49 + 0.10
treatrn cnt with 200 IJ.gfml hydroxy lomine, killed 50 per cent of
contro! population, n = 2.2 :.. 0.7, Do = 2.57 ± 0.22
'l'llird ponel.
o---o
X - - -X
~ --- ~
e ---·
:;
contro( s urvival, n -- 3.7 -f: 1.1, Do = 1.83 L 0. 12
~ hour post-irradiation trea tmen t witb O. l !J-g •ml cytosin e a ra binosid e, l O· per cent of contro! unirradiuted cells killed b y the
treotmrut, n = 5.5 .!. 0.8, Do = l. Bl - 0.06
t reatm ent wi th 0.5 !-I@:Jnll ry tosine arah inMid e. killed 10 per rc- nt
o f contro! po,Julation , n
·1.1
l A , Do ~ l.BJ _ 0. 13
lreatment -. it h 1.0 )ig /ml r ytosiue arabi no~idr. killrd 2.) per cr ut
o f <·ontrol populat io n, n
3.0 - 1. 1. •- l. 93 .:. 0.1 7
''"'· / .; 1.
.-;.,,.a.
S(lllitù Ct969l 5 , :167·:175.
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.,,.1_
.,,
l nhibiwr, o(
n\
l .w ntlwsi.,.
l
l
l
I n .Ht"! .a rrll..: it ha ~ lu·t·n :ohown tlwt tlwn· i::- rnu rlr 'ariation 111 tlw
rl'spon~t· t o inhibiton. of DJ\ A l'ynllws is li•llowing À-ra~ irradiation (\\· EIS~
& TOLMACII , 19(li) dqH'nding upun tlw partirular inhihitnr u sNI. Tlw failuro ·
of h ydruxyurt>a t eo alter tlw re;,pon:'f' ol' a>-~·nchronnu s CHC to U\ Uf!ht
{AIILETT. J%7) ~'as conlirm c·d by tht· u si' o f rxcPss th ymid inl' (K«H:h Li g h l),
t·ytosÌJH' araloiJw:-.id .. (.1\.oclr Light) nnd bvdrvxv lamirw (Hopki n~o & " ' il liam-.). Thr rt'!'lllt!' are illtts l ralt' d in Fig. :L
l
l
l
l
l
l
l
Any n·pair i ~ lilely lo ÌJrvnh P Lh•· >-v utlwsi t- of Ili''' D l\ A anù t ho ~··
1->a uw i11lr i!J i t or;. w ere Ut'X l s how11 t n l11· \\ i thnnt PIJ'Prl o n t>vnduorr i::wtl Cf' li ~
in tlr•• S pha-.p nf thr l'PII r~ ciP (Fig. 4). 'y rr cbronis('(l populationt- of t•dls ,,·er.oLtaiuNI !J~· use of u dou h l•· hloc k "ith PX CI'!-.t' tlr y millint· al 25 m l\·l (CAL-\ VAZI , ScuENK & BooTSMA, 19C.b). l'hP syn dum ry uf thc- pnpu lation!- is s iro\\ 11
m Fig. :l with tlw ultra-Yiolet rcspom,r· al tim t·;; aflf·r tlw n •lf'a;,t• of t lw IWCO Ji d
l
Fi)!. :l.
l
- The pruductinn of synçhruni ,l•cl
population• of CliC h) thr uppli·
l'ntion of a douhlt• blol·k of I'XCC'•'
l
tb) ruidinr (2.5 rnllt ) un d the r«>•·
pomi' 11f tht•se rell b to ultru-viol(•l
light. The platini! rflicirnq of
unirradiatl'd cells nt rn~:h J.lh"'" uf
th f cl' li cyrlr \\&!- tok eu as l UU 1111
~Ur\ ival \du· u euutputiu~ J'(fÌilb•.
Liu eF fitted hy l'VI'.
Top pane/.
0 - - -0
e---e
<·l'llulur
ruultipliri t ~
pcrcrn t lnbellcd celi,
11s df'lermiued hy au turadiogruph~
Bouom
pan~l.
0 - - -0
•L•---·
*---*
,,
uv tllPQSUtt( (M«tt'''t
l
~·
bllrvivul of celJ P thn•c•
hour• after th l' rdea•l'
of tltc tb ymidin <• hlot·k
(
phusr celi.)
~urviva l al 6 hour•
(G2 phs.H· celi•)
s urvivnl ot 8 hour..
plnt>t' cd h,)
tbi s data hn • het•u
ndju <tt•d for multipliril)
(St..,CLAIH
&
>\JoRTIIN. 1965).
(= Cl
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A IILETI'
373
tby midine block whicb are considcred to be at S, G2 an d ca (• h a·;('~ uf t l ,.
cell cycle. The response of cells a t these thrce s tages is sr~·n o l w ~o
to those alrcady puhlished (SrNCLAIR & MORTON , 1965) with 1 lls in ti c \,i
phase of tbc ceU cycle exhibiting t be grcatest rrsietniiN'.
Di.~cu ss iort.
Tbc cviclcnce of interaction hctween UV a nd gammu irradiation "
tbe c lone F of CHC ie takeo to indicate t he prcsencc of r(•pair p rocesscs fo\"
UV iod ucetl lethal lcsions in this materia! ( ABLETT, 1968).
The negative resulte with inbibitors of DNA synthesis, on asynchronous or synchronous cells, confìrm the earlier observatione wi th hyd roxyurea
(ArtLETT , 1967). Thie result might be due to the fact t hat while thrse compouncls are capablc of iohibiting gross DNA synthesis, poly merase activity
is stili maintained a t a sufficient level to achieve the synthesis of new rnateria l
requirrd for the reconstructiou of damaged DNA. In this connection HaNAWAL'r et al. (1968) bave shown that the polymerascs in olvcd in semi-conservativt' replicatioo nnd the repair rr plication mod(• may not be iclcntical,
they may, therefort>, have different seositivities to inhibitors. In HeLa celle
C LEAVER (1969) hae shown t hat a wide gr oup of inhibitors of D NA syntheeis
inhibit norma! synthesis (semi-conser vative r eplication) but bave no effrct
on rcpair .r eplication.
The observations made with ethidium bromide ehow thal this compound
enhancee survival when applied at non-toxic levele to t he poet-irradiation
medium and ie the onJy evidence from metaholie s tudiee to support the
cooerpt of repair of UV induced poteotially lc tha l lesione in C HC. I ts
action on celi survival ie clearly unlike that of aetiomycin O or a<'rifiavinc
( AnLETT, 1967) even though it may bave eimilar effects on the biochemistry
of the cell. Thus it. forme reversible eomplexes wi th nucleie acide, inhibits
DNA polymcrase and DNA directed RNA eyothesie (WARJNG , 1966). A
poesible explanatiou for ite •·ffect ie t hat it mig ht prolong division time a nd
permit a gr eater period for the repair p~cesses to hring ahout t•nhanccd
!lurvival. In sca urchin egge ethidium bromide prolongs the pPriod of D N A
synthcsie (V ACQU I E R & BR ACRET , 1969) euggestin g a prolongation of celi
eycle t ime. T he observatione with this drug have been duplicat ed with the
diploid zygospores of tbc greco alga Chlttmy domonos reinhardii, hcre both
an f•nhancemt•nt and reduction in survival are aehicved res pectively a t Jessrr
;md g reater hut n ev~>rtbel ess non-toxic levele of thl' drug (ARLETT. unpublishr d results).
T he a bsf'nce of a n r ffeet of cnfl"ei ne in CHC (A ULETT, 1967) is ronfirmr d
hy a positivi' Pffect on Hd.a cclls with the
., same ha tch ol' chemical. This
s u ~gcs ts t hat tlle pri'S I'MC or nbsencc nf an''i>lfPct of lhis drug which iubihit11
l tw . / xl . "'" ~"'· Sno11 1t'r t 1Ufi1)) 5. :lfii ·:l7.i.
371
l
ACT(III~
,H'Ft 1 11 t\(,
t.n.t,l
I.AII
1'1111'10"'1
"~1\'n
\
endonudt•as<> acti\ÌI ~ ( H OLL J.AN-Dl'SSOl'-. JI.)(J /) might dt• dtw lO a Sp t'<'lfirit y of actiuu nnt 1o an y dillc rcu ce:-; in 1cpuir abiliL).
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H l'La aud CliC in r('sp nmw t o c afJ'eint· dra11;.
l
atll'ntiou to tlw diflic uli y of l1riug ing t og•· th1:r tbt• t wo PXprrim!'ut al •·n d
po ints of ultra' iolet re!-ptm H·. LlH' h iocbt•tn ical s tudi r.., and t Ili' Ct>ll su n i' al
l
l
Tltt• difl t>rcn rt>;. Let,q·en
s tudi es.
Thus tht• pr<Wl'!.St·s i n ,.o h c·tl i 11
~"Xcisiou rt·pair h a' 1· )H•cu s bowu
tu n·m"' l'50 p rr <·•·n t of th1· dtm<·r;. intlu red in H •·Ln r •·ll;. (Jh;;GAN, Tno~Jo. o
& CAnRJEn , J 96B) uur cuffeint · wu;. \1 ith out l'f:l'rel ou this phcnomroou .
Cu;A\E H (1Qh9) ha~ al;.n s llll\l ll si milar rl';m ll ~ with Jl t•La l'l'Il:- wlwn l11·
sttHlit•d the highly l'orn·lat !"d phenonH' lW of ri'Jiair n·p lication and un;.<·hl'dull'd DI\ A synth rsi!-., aga in , rafl'f'int· w a!-. wit huut t•fl'l'et. N t'i l hl'r ~roup of
au 1 hor~o~ indi('a l t'd if c aA'I'inl' nwdified N· li -;un i' al iti this tua t t· ri al. ho,.-,·, t•r.
tht· results ohtauwd wilh tlw 1\J.H.E. st raiu of ll<•la el'll,.; would intlic;aiP
that thi~o~ i ~;. in fa c l, ti w cm•<·.
Thc ri'SJHill !<<' o f tlWIHW L ('l'lls 11• cafi'•·Ìul' i;. <dso rl'ln aut Ile· n · ~<i u cc· t h i;;
m all'riai j., la<·kin~ in r r p uir n·p]ieatinn (CLEA\Tll. l 9(17) ami ••xcis io n r ep air
J96(1) hu t shows a n ·d uri io u in ~urvi' al \1 lH·n ruffc·illc· i ~ addrd Lo
tL1• p ost irratlia tiun mPclium ( H AUTU. 1967). Tt ha,. IH·c•u s u gge.- tc·d that.
wbcrr pffc•cti vl', rn n'l·inc· is interf.. rin g with sonw n· pair proet'ss rlis-li';;M;
(1\.J, t MEK,
from excisiou re p air or n ' pair rPp licatio u . p<·rh a p~ tlw r c·c·umhinatio nal form
of rc p a ir (Cu;AVEH . t h f'Ht' pru<·c·edin.gs).
CJ-H:J 1113 ) thcm lw c·ontra!<trd witla
H r La ami m uu"l' L C<'ll" in fa ilinl! to <"x hiiJit a r eco ml1inat inn n •p air pm cc·~'
'dtic h j.., sl'n s ilin· 111 cafi't•ÌJH'. This 1-(I'Onp of rNmlt R rnight, ho\IC'Vc· r. s u gf!c·;;t
that tllt' !Jiocllt'mical r f'"ou lt , an' in 1111 wa~ corrclat<"d \1 ith c eli >. Il n i' al.
Thr data of Ct.EAY JW (1Wt8h) l': lw wing tlw mudt rPÙLH'f'd LW sciH·clnlt·d D '\.
syn tlw;;i~-> in c· a,!':- uf X(•rodrrma p ifl,llll'lllnsum su ppurts t h •• alt t•rn a l i' c· MI~­
gPs tion . l l nJi •r·tun a tPi y th P cultura l diflic·u ltic·;. with t bi!' materia! lt<l\ c· tlttl
madr it p ossiiJle, ac; }l'l. IO d\'lnmin•· if c••·ll, frum Xcrutlc·rmu pa t i••nlb un·
n wrl' s r·us iti' c• t o UV than c·PIIs from n o r ma l pati1•nts.
It i:- rl<'ar that tlt~• r<' Ì !> co u~ id era l.l•· scopP for fut ure invf·s ti ~a tillll b
whic•h atu·mpt t o briug t ogetlwr crll ~>uni,·al and hi oclwmi(~al d a t a for tlw
photnhiulogintl r rR[HillSI' of m a mm u lian cclls.
I a111 ìndeiJ lt'cl l o !>1r~. J , Pottcr a nd \ lr. \. H. <~ould fur t')o.perl let·hnì<'al lt~Eìstnuc·r.
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HEFI-.RE \ CES
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