Detection of DNA damage induced in vivo following exposure of rats to carcinogens.

作者：Gary L. Petzold, James A. Swenberg · 发表于：PubMed · 年份：1978 · 被引用次数：138 · 研究领域：Carcinogens and Genotoxicity Assessment、DNA Repair Mechanisms、Cancer therapeutics and mechanisms

ABSTRACTAnalkalineelutionassaypreviouslyusedtodetectsingle-strandbreaksinDMAofculturedmammaliancellshasbeenmodifiedtoallowtheanalysisofDMAdamageinvariousorgansofratsfollowingexposuretochemicalcarcinogens.Priortoexposure,theDMAofneonatalanimalswaslabeledwith[3H]thymidine.DNAdamagewasassessedinliver,lung,thymus,brain,kidney,stomach,duodenum,colon,bonemarrow,andmammarygland.Dimethylnitrosamine,diethylnitrosamine,4-nitroquinolme1-oxide,2-acetylaminofluorene, N-hydroxyacetylamino-fluorene,aflatoxinB,,1,2-dimethylhydrazine,azoxymeth-ane,benzidine-HCI,and7,12-dimethylbenz(a)anthraceneinducedthegreatestextentofDNAdamageintargetorgansforcarcinogenicity.Invivoexposuretoseveraldirect-actingalkylatingagents,includingW-methyl-N'-ni-tro-N-nitrosoguanidine, N-methyl-N-nitrosourea, N-ethyl-N-nitrosourea, methylmethanesulfonate, andethylmethanesulfonate, causedsignificantDNAdamageintargetandnon-targettissues.Dose-relatedincreasesintheDNAelutionpatternswereobserved.DNArepairtime,asmeasuredbythereturntoanormalelutionpattern,variedfromaslittleas24hrfor4-nitroquinoline1-oxidetoaslongas7daysfordimethylnitrosamine. TheinvivoDNAdamage-alkalineelutionassayoffersarapidandreliableassayforassessmentoftheabilityofacompoundtoinduceDNAdamage.INTRODUCTIONManycarcinogens havebeenshowntointeractwithcellularDNAinanumberofwaysincludingalkylation,intercalation,cross-linking,andphosphotriesterformation.Theseandothercarcinogen-macromolecule interactionshavebeenreviewedrecently(7,10,19).Invivoexposuretocarcinogensa...