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时间:2019-08-04
《473-In vitro Mammalian Chromosome Aberration Test》由会员上传分享,免费在线阅读,更多相关内容在学术论文-天天文库。
1、473Adopted:21stJuly1997OECDGUIDELINEFORTHETESTINGOFCHEMICALSInVitroMammalianChromosomeAberrationTestINTRODUCTION1.Thepurposeoftheinvitrochromosomeaberrationtestistoidentifyagentsthatcausestructuralchromosomeaberrationsinculturedmammaliancells(1)(2)(3).Structurala
2、berrationsmaybeoftwotypes,chromosomeorchromatid.Withthemajorityofchemicalmutagens,inducedaberrationsareofthechromatidtype,butchromosome-typeaberrationsalsooccur.Anincreaseinpolyploidymayindicatethatachemicalhasthepotentialtoinducenumericalaberrations.However,this
3、guidelineisnotdesignedtomeasurenumericalaberrationsandisnotroutinelyusedforthatpurpose.Chromosomemutationsandrelatedeventsarethecauseofmanyhumangeneticdiseasesandthereissubstantialevidencethatchromosomemutationsandrelatedeventscausingalterationsinoncogenesandtumo
4、ursuppressorgenesofsomaticcellsareinvolvedincancerinductioninhumansandexperimentalanimals.2.Theinvitrochromosomeaberrationtestmayemployculturesofestablishedcelllines,cellstrainsorprimarycellcultures.Thecellsusedareselectedonthebasisofgrowthabilityinculture,stabil
5、ityofthekaryotype,chromosomenumber,chromosomediversityandspontaneousfrequencyofchromosomeaberrations.3.DefinitionsusedaresetoutintheAnnex.INITIALCONSIDERATIONS4.Testsconductedinvitrogenerallyrequiretheuseofanexogenoussourceofmetabolicactivation.Thismetabolicactiv
6、ationsystemcannotmimicentirelythemammalianinvivoconditions.CareshouldbetakentoavoidconditionswhichwouldleadtopositiveresultswhichdonotreflectintrinsicmutagenicityandmayarisefromchangesinpH,osmolalityorhighlevelsofcytotoxicity(4)(5).5.Thistestisusedtoscreenforposs
7、iblemammalianmutagensandcarcinogens.Manycompoundsthatarepositiveinthistestaremammaliancarcinogens;however,thereisnotaperfectcorrelationbetweenthistestandcarcinogenicity.Correlationisdependentonchemicalclassandthereisincreasingevidencethattherearecarcinogensthatar
8、enotdetectedbythistestbecausetheyappeartoactthroughmechanismsotherthandirectDNAdamage.PRINCIPLEOFTHETESTMETHOD6.Cellculturesareexposedtothetestsubstancebothwit
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