A clonal study of the reversible inhibition of muscle differentiation by the halogenated thymidine analog 5-bromodeoxyuridine☆
[摘要] Thethymidineanalog5-bromodeoxyuridine(BUdR)iswellknownforitsmutageniceffectswhenincorporatedinDNA.Similarly,BUdRhasbeenreportedbyseveralworkerstoinhibitcytodifferentiationwhenappliedduringthecellproliferativephase.Wehaveobservedthatrelativelylowlevels(ca10−6M)ofBUdR,IUdR,ClUdR,andBCdRallcauseagradualchangeincellmorphology,andinhibitthefusionofcellstoformsyncytiainmuscleclones,butdonotinterferewithproliferationofmononuclearcells.Theinhibitionofdifferentiationcanbereversedbyfurthercelldivisionintheabsenceoftheanalog.Afterseveraldays,thisresultsinclonalcultureswhichareindistinguishablefromuntreatedcontrolsbothintermsoftotalnumberofclonesandoftheproportionofcloneswhicharemyogenic;thusthedrugsarenotactingeitherbycellselectionormutagenesis.BUdRisincorporatedintoDNAinplaceofthymine,itseffectondifferentiationcanbecompetitivelypreventedbysimultaneousinclusioninthemediumofTdRorcompoundsreadilyconvertibletoTdR,andithasnodetectableeffectonpostmitoticcells(musclefibers).AlthoughthissuggeststhatBUdRexertsitseffectondifferentiationfromasiteintheDNA,aneffectoncellmetabolismatsomeotherlevelcannotberuledout.
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[效力级别] [学科分类] 生物科学(综合)
[关键词] RNase;ribonuclease;DNase;deoxyribonuclease;PTA;phosphotungstic acid;FUdR;5-fluorodeoxyuridine;ClUdR;5-chlorodeoxyuridine;BUdR;5-bromodeoxyuridine;TdR;thymidine;BCdR;5-bromodeoxycytidine;IUdR;5-iododeoxyuridine;BUR;5-bromouridine;BU;5-bromouracil;OHMeUdR;5-hydroxymethyldeoxyuridine;2;6-DAPdR;2;6-diaminopurine deoxyriboside;5-MeCdR;5-methyldeoxycytidine;T;thymine;CdR;deoxycytidine;UdR;deoxyuridine;UR;uridine;U;uracil;TR;thymine riboside;AdR;deoxyadenosine;3-MeCdR;3-methyldeoxycytidine [时效性]