© 1985 Oxford University Press
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Evidence for a major premutagenic ethyldeoxythymidine-DNA adduct in an in vivo system: N-nitroso-N-ethylurea-treated Salmonella typhimurium
1Department of Biochemistry, New York University Dental Center New York, NY 10010
2Department of Environmental Medicine, New York University Medical Center New York, NY 10016, USA
3To whom reprint requests should be sent: Department of Biochemistry, New York University Dental Center, New York, NY 10010, USA
Mutagenesis induced by N-nitroso-N-ethylurea (NEU) was assayed in four strains of Salmonella typhimurium which are known to be reverted to histidine prototrophy by mutations at A-T base pairs and by extragenic suppression. NEU-induced revertants were characterized for the presence of extragenic suppressors by their sensitivities to the histidine analogue, thiazolealanine. In strains carrying the plasmid, pKM101, only a small percentage of the revertants was due to suppressors, indicating that NEU gives rise to a major pre-mutagenic adenine or thymidine-DNA adduct. In strains without plasmid, mutagenesis was much less efficient and resulted mainly from suppressors. Apparently error-prone DNA-repair plays an important role in mutagenesis via the A or T-DNA adduct in the plasmid-containing strains. Ethylmethanesulfonate (EMS), a mutagen known to form ethyladenines but not ethylthymidines, induced mutagenesis that resulted mainly from suppressors in all strains, and there was little inter-strain difference in the sensitivity to EMS. Since NEU, but not EMS, forms ethylthymidines in appreciable yield, and only NEU induced high percentages of revertants with mutations at A-T base pairs, it appears that at least one ethylthymidine is a major premutagenic adduct in NEU-induced mutagenesis.