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时间:2019-08-04
《471-Bacterial Reverse Mutation 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、471Adopted:21stJuly1997OECDGUIDELINEFORTESTINGOFCHEMICALSBacterialReverseMutationTestINTRODUCTION1.Thebacterialreversemutationtestusesamino-acidrequiringstrainsofSalmonellatyphimuriumandEscherichiacolitodetectpointmutations,whichinvolvesubstitution,additio
2、nordeletionofoneorafewDNAbasepairs(1)(2)(3).Theprincipleofthisbacterialreversemutationtestisthatitdetectsmutationswhichrevertmutationspresentintheteststrainsandrestorethefunctionalcapabilityofthebacteriatosynthesizeanessentialaminoacid.Therevertantbacteria
3、aredetectedbytheirabilitytogrowintheabsenceoftheaminoacidrequiredbytheparentteststrain.2.Pointmutationsarethecauseofmanyhumangeneticdiseasesandthereissubstantialevidencethatpointmutationsinoncogenesandtumoursuppressorgenesofsomaticcellsareinvolvedintumourf
4、ormationinhumansandexperimentalanimals.Thebacterialreversemutationtestisrapid,inexpensiveandrelativelyeasytoperform.Manyoftheteststrainshaveseveralfeaturesthatmakethemmoresensitiveforthedetectionofmutations,includingresponsiveDNAsequencesatthereversionsite
5、s,increasedcellpermeabilitytolargemoleculesandeliminationofDNArepairsystemsorenhancementoferror-proneDNArepairprocesses.Thespecificityoftheteststrainscanprovidesomeusefulinformationonthetypesofmutationsthatareinducedbygenotoxicagents.Averylargedatabaseofre
6、sultsforawidevarietyofstructuresisavailableforbacterialreversemutationtestsandwell-establishedmethodologieshavebeendevelopedfortestingchemicalswithdifferentphysico-chemicalproperties,includingvolatilecompounds.3.DefinitionsusedaresetoutintheAnnex.INITIALCO
7、NSIDERATIONS4.Thebacterialreversemutationtestutilisesprokaryoticcells,whichdifferfrommammaliancellsinsuchfactorsasuptake,metabolism,chromosomestructureandDNArepairprocesses.Testsconductedinvitrogenerallyrequiretheuseofanexogenoussourceofmetabolicactivation
8、.Invitrometabolicactivationsystemscannotmimicentirelythemammalianinvivoconditions.Thetestthereforedoesnotprovidedirectinformationonthemutagenicandcarcinogenicpotencyofasubstanceinmammals.5.Thebacterialreverse
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