475-Mammalian Bone Marrow Chromosome Aberration Test

《475-Mammalian Bone Marrow 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、475Adopted:21stJuly1997OECDGUIDELINEFORTHETESTINGOFCHEMICALSMammalianBoneMarrowChromosomeAberrationTestINTRODUCTION1.Themammalianinvivochromosomeaberrationtestisusedforthedetectionofstructuralchromosomeaberrationsinducedbytestcompoundsinbonemarrowcellsofanima

2、ls,usuallyrodents(1)(2)(3)(4).Structuralchromosomeaberrationsmaybeoftwotypes,chromosomeorchromatid.Anincreaseinpolyploidymayindicatethatachemicalhasthepotentialtoinducenumericalaberrations.Withthemajorityofchemicalmutagens,inducedaberrationsareofthechromatid-

3、type,butchromosome-typeaberrationsalsooccur.Chromosomemutationsandrelatedeventsarethecauseofmanyhumangeneticdiseasesandthereissubstantialevidencethatchromosomemutationsandrelatedeventscausingalterationsinoncogenesandtumoursuppressorgenesareinvolvedincancerinh

4、umansandexperimentalsystems.2.DefinitionsusedaresetoutintheAnnex.INITIALCONSIDERATIONS3.Rodentsareroutinelyusedinthistest.Bonemarrowisthetargettissueinthistest,sinceitisahighlyvascularisedtissue,anditcontainsapopulationofrapidlycyclingcellsthatcanbereadilyiso

5、latedandprocessed.Otherspeciesandtargettissuesarenotthesubjectofthisguideline.4.Thischromosomeaberrationtestisespeciallyrelevanttoassessingmutagenichazardinthatitallowsconsiderationoffactorsofinvivometabolism,pharmacokineticsandDNA-repairprocessesalthoughthes

6、emayvaryamongspeciesandamongtissues.Aninvivotestisalsousefulforfurtherinvestigationofamutageniceffectdetectedbyaninvitrotest.5.Ifthereisevidencethatthetestsubstance,orareactivemetabolite,willnotreachthetargettissue,itisnotappropriatetousethistest.PRINCIPLEOFT

7、HETESTMETHOD6.Animalsareexposedtothetestsubstancebyanappropriaterouteofexposureandaresacrificedatappropriatetimesaftertreatment.Priortosacrifice,animalsaretreatedwithametaphase-arrestingagent(e.g.,colchicineorColcemid®).Chromosomepreparationsarethenmadefromth

8、ebonemarrowcellsandstained,andmetaphasecellsareanalysedforchromosomeaberrations.1/8475OECD/OCDEDESCRIPTIONOFTHEMETHODPreparationsSelectionofanimalspecies7.Rats,miceandChinesehamstersareco