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Main Title Mutation Spectrum of a Binary Mixture of Mutagens (Methapyrilene and Sodium Azide) in Strain TA1535 of Salmonella.
Author Shelton, M. L. ; Ashby, J. ; DeMarini, D. M. ;
CORP Author Health Effects Research Lab., Research Triangle Park, NC. ;ZENECA Central Toxicology Labs., Cheshire (England).
Publisher c1994
Year Published 1994
Report Number EPA/600/J-94/409;
Stock Number PB95-125373
Additional Subjects Mutation ; Mutagens ; Salmonella typhimurium ; Methapyritene ; DNA repair ; Necleic acid hybridization ; Carcinogens ; DNA replication ; Liver neoplasms ; Reprints ; Sodium azide
Library Call Number Additional Info Location Last
NTIS  PB95-125373 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 8p
Methapyrilene (MP) is a rat-liver carcinogen and cocarcinogen that exhibits a narrow spectrum of mutagenic activity in Salmonella typhimurium, inducing only a 2-fold increase in revertants only in the base-substitution strain TA1535; it also enhances the mutagenic activity of sodium azide (NaN3) in the same strain. To examine the effects of MP at the molecular level, the authors used the colony probe hybridization procedure developed by Cebula and Koch (Mutation Res., 229 (1990) 79-87) to identify the base substitutions in approximately 800 background, MP-, NaN3-, and MP + NaN3- induced revertants of the hisG46 allele of strain TA1535. The predominant mutation in all 4 mutation spectra was a CC---CTC transition. The results suggest a mechanism by which MP enhances the infidelity of the DNA replication complex or inhibits a DNA repair or proofreading function, resulting in the production of more of the same error that occurs normally and that is also induced by NaN3. Such a mechanism might be the basis for the carcinogenic and cocarcinogenic activities of MP. To our knowledge, this is the first report of the molecular analysis of mutants produced by exposure of cells to a binary mixture of mutagens. (Copyright (c) 1994 Elsevier Science B.V.).