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时间:2019-08-04
《474-Mammalian Erythrocyte Micronucleus 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、474Adopted:21stJuly1997OECDGUIDELINEFORTHETESTINGOFCHEMICALSMammalianErythrocyteMicronucleusTestINTRODUCTION1.Themammalianinvivomicronucleustestisusedforthedetectionofdamageinducedbythetestsubstancetothechromosomesorthemitoticapparatusoferythroblastsbyanalysisoferythrocytesassampledinbonemar
2、rowand/orperipheralbloodcellsofanimals,usuallyrodents.2.Thepurposeofthemicronucleustestistoidentifysubstancesthatcausecytogeneticdamagewhichresultsintheformationofmicronucleicontaininglaggingchromosomefragmentsorwholechromosomes.3.Whenabonemarrowerythroblastdevelopsintoapolychromaticerythroc
3、yte,themainnucleusisextruded;anymicronucleusthathasbeenformedmayremainbehindintheotherwiseanucleatedcytoplasm.Visualisationofmicronucleiisfacilitatedinthesecellsbecausetheylackamainnucleus.Anincreaseinthefrequencyofmicronucleatedpolychromaticerythrocytesintreatedanimalsisanindicationofinduce
4、dchromosomedamage.4.DefinitionsusedaresetoutintheAnnex.INITIALCONSIDERATIONS5.Thebonemarrowofrodentsisroutinelyusedinthistestsincepolychromaticerythrocytesareproducedinthattissue.Themeasurementofmicronucleatedimmature(polychromatic)erythrocytesinperipheralbloodisequallyacceptableinanyspecies
5、inwhichtheinabilityofthespleentoremovemicronucleatederythrocyteshasbeendemonstrated,orwhichhasshownanadequatesensitivitytodetectagentsthatcausestructuralornumericalchromosomeaberrations.Micronucleicanbedistinguishedbyanumberofcriteria.Theseincludeidentificationofthepresenceorabsenceofakineto
6、choreorcentromericDNAinthemicronuclei.Thefrequencyofmicronucleatedimmature(polychromatic)erythrocytesistheprincipalendpoint.Thenumberofmature(normochromatic)erythrocytesintheperipheralbloodthatcontainmicronucleiamongagivennumberofmatureerythrocytescanalsobeusedastheendpointoftheassaywhenanim
7、alsaretreatedcontinuouslyfor4weeksormore.6.Thismammalianinvivomicronucleustestisespeciallyrelevanttoassessingmutagenichazardinthatitallowsconsiderationoffactorsofinvivometabolism,pharmacokineticsandDNA-repairprocessesalthoughthesemayvaryamongspecie
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