471-Bacterial Reverse Mutation Test

《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