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【英文标准名称】:StandardPracticeforInVivoRatHepatocyteDNARepairAssay
【原文标准名称】:鼠体内肝细胞DNA修复化验的标准作法
【标准号】:ASTME1398-1991(2008)
【标准状态】:现行
【国别】:美国
【发布日期】:1991
【实施或试行日期】:
【发布单位】:美国材料与试验协会(US-ASTM)
【起草单位】:F04.16
【标准类型】:(Practice)
【标准水平】:()
【中文主题词】:
【英文主题词】:DNA(deoxyribonucleicacid);Geneticexamination;HepatocyteDNArepairassay;Rats;Thymidine
【摘要】:MeasurementofchemicallyinducedDNArepairisameansofassessingtheabilityofachemicaltoreachandaltertheDNA.DNArepairisanenzymaticprocessthatinvolvesrecognitionandexcisionofDNA-chemicaladducts,followedbyDNAstrandpolymerizationandligationtorestoretheoriginalprimarystructureoftheDNA(6).ThisprocesscanbequantitatedbymeasuringtheamountoflabeledthymidineincorporatedintothenuclearDNAofcellsthatarenotinS-phaseandisoftencalledunscheduledDNAsynthesis(UDS)(7).NumerousassayshavebeendevelopedforthemeasurementofchemicallyinducedDNArepairinvariouscelllinesandprimarycellculturesfrombothrodentandhumanorigin(4).TheprimaryculturerathepatocyteDNArepairassayhasproventobeparticularlyvaluableinassessingthegenotoxicactivityofchemicals(8).Genotoxicactivityoftenresultsfrommetabolitesofachemical.Theinvitrorathepatocyteassayprovidesasysteminwhichametabolicallycompetentcellisalsothetargetcell.Mostotherinvitroshort-termtestsforgenotoxicityemployaratliverhomogenate(S-9)formetabolicactivation,whichdiffersmarkedlyinmanyimportantwaysfromthepatternsofactivationanddetoxificationthatactuallyoccurinhepatocytes.AnextensiveliteratureisavailableontheuseofinvitroDNArepairassays(9-19).AfurtheradvancewasthedevelopmentofaninvivorathepatocyteDNArepairassayinwhichthetestchemicalisadministeredtotheanimalandtheresultingDNArepairisassessedinhepatocytesisolatedfromthetreatedanimal(20).NumeroussystemsnowexisttomeasurechemicallyinducedDNArepairinspecifictissuesinthewholeanimal(4).Theaverageofinvivoassaysisthattheyreflectthecomplexpatternsofuptake,distribution,metabolism,detoxification,andexcretionthatoccurinthewholeanimal.Further,factorssuchaschronicexposure,sexdifferences,anddifferentroutesofexposurecanbestudiedwiththesesystems.Thisisillustratedbythepotenthepatocarcinogen2,6-dinitrotoluene(DNT).Metabolicactivationof2,6-DNTinvolvesuptake,metabolismbytheliver,excretionintothebile,reductionofthenitrogroupbygutflora,readsorption,andfurthermetabolismbytheliveronceagaintofinallyproducetheultimategenotoxicant(21).Thus,2,6-DNTisnegativeintheinvitrohepatocyteDNArepairassay(22)butisaverypotentinducerofDNArepairintheinvivoDNArepairassay(23,24).Aproblemwithtissue-specificassaysisthattheymayfailtodetectactivityofcompoundsthatproducetumorsinothertargettissues.Forexample,noactivityisseenintheinvivoDNArepairassaywiththepotentmutagenbenzo(a)pyrene(BP),probablybecauselimitedtissuedistributionandgreaterdetoxificationintheliveryieldstoofewDNAadductstoproduceameasurableresponse(3).Incontrast,BPisreadilydetectedinthelesstissue-specificinvitrohepatocyteDNArepairassay(11).AnextensiveliteratureexistsontheuseoftheinvivohepatocyteDNArepairassay(1-3,5,9,25-33).1.1ThispracticecoversatypicalprocedureandguidelinesforconductingtheratinvivohepatocyteDNArepairassay.Theprocedurespresentedherearebasedonsimilarprotocolsthathave......
【中国标准分类号】:B41
【国际标准分类号】:11_220
【页数】:9P.;A4
【正文语种】:英语