MUTAGENIC AND DNA-DAMAGING EFFECTS OF N-ALKYL-N-(α-ACETOXYALKYL) NITROSAMINES, MODELS FOR METABOLICALLY ACTIVATED N, N-DIALKYLNITROSAMINES

• Published in: GANN Japanese Journal of Cancer Research Vol. 70; no. 5; pp. 663 - 670
• Main Authors: MOCHIZUKI, Masataka, SUZUKI, Emako, ANJO, Takako, WAKABAYASHI, Yuko, OKADA, Masashi
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Cancer Association 01.01.1979
• Subjects: Bacillus subtilis - drug effects; Bacteria; DNA Repair - drug effects; DNA, Bacterial - genetics; Dose-Response Relationship, Drug; Escherichia coli - drug effects; Metabolic activation; Microbial Sensitivity Tests; Models, Biological; Mutagenesis; Mutagens; N, N-Dialkylnitrosamine; N-Alkyl-N-(α-acetoxyalkyl) nitrosamine; Nitrosamines - pharmacology; Salmonella typhimurium - drug effects
• ISSN: 0016-450X
• DOI: 10.20772/cancersci1959.70.5_663

Mutagenic and DNA-damaging effects of a series of N, N-dialkylnitrosamines monosubstituted at the α-carbon with an acetoxyl group were tested in Salmonella typhimurium, Escherichia coli, and Bacillus subtilis in the absence of metabolic activation system. The compounds comprised 8 N-alkyl-N-(acetoxymethyl)nitrosamines (alkyl=methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, or tert-butyl) and N-butyl-N-(1-acetoxybutyl)nitrosamnie. All the compounds, except one with a tert-butyl group, gave positive results in these mutagenicity and repair tests. Presumed release of alkyl cations from the corresponding α-acetoxy derivatives by hydrolysis and heterolysis caused mutagenic and DNA-damaging effects in the bacteria. Structure-activity correlation of the compounds was noted in these tests and discussed in regard to the mutagenicity with metabolic activation and carcinogenicity of N, N-dialkylnitrosamines. The results support the hypothesis that α-carbon hydroxylation is one probable mechanism involved in the metabolic activation of N, N-dialkylnitrosamines.