Studies on chemical carcinogens and mutagens. XXIX. Mutagenic N-trimethylsilylmethyl-N-nitrosourea as a biological alkylating agent equivalent to N-methyl-N-nitrosourea (MNU).
N-Trimethylsilylmethyl-N-nitrosourea (TMS-MNU), a silicon analogue of N-neopentyl-N-nitrosourea (neoPNU), was assayed for mutagenicity and/or cytotoxicity on a series of E. coli B tester strains, S. typhimurium TA100, Chinese hamster V79, and cultured murine leukemia L1210 cells. All the biological activities demonstrated in this study reveal that this nitrosourea is a biological methylating agent equivalent to N-methyl-N-nitrosourea (MNU) but definitely distinguished from all the other alkylnitrosoureas examined so far, including neoPNU (the carbon analogue of TMS-MNU). The proposed molecular mechanism is that trimethylsilylmethanediazohydroxide is produced by hydrolytic activation of TMS-MNU and undergoes a nucleophilic cleavage of the Si--CH2 chemical bond at a high rate to form methanediazohydroxide (the reactive intermediate of MNU) which, in turn, methylates the informational biopolymer leading to mutagenesis.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004926:Escherichia coli / Q000187:drug effects; D007939:Leukemia L1210 / Q000473:pathology; D008168:Lung; D008770:Methylnitrosourea / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity*; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens; D009154:Mutation; D009607:Nitrosourea Compounds / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects; D012825:Silicon / Q000633:toxicity*; D014297:Trimethylsilyl Compounds / Q000494:pharmacology / Q000633:toxicity*
D009153:Mutagens; D009607:Nitrosourea Compounds; D014297:Trimethylsilyl Compounds; C045827:N-trimethylsilylmethyl-N-nitrosourea; D008770:Methylnitrosourea; D012825:Silicon