473-In vitro Mammalian Chromosome Aberration Test

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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