Detection of a deuterium isotope effect in di- and trisubstituted alkylphenylnitrosoureas. An SCE study in Chinese hamster V79-E cells.
The genotoxicity of 1-methyl-3-phenyl-1-nitrosourea (MPNU), 1-methyl-3-(p-chlorophenyl)-1-nitrosourea (C1-MPNU), 1-ethyl-3-phenyl-1-nitrosourea (EPNU), 1,3-dimethyl-3-phenyl-1-nitrosourea (DMPNU) and their derivatives substituted by deuterium in different positions was studied using sister chromatid exchange (SCE) induction in Chinese hamster V79-E cells. Deuterium substitution in the 1-methyl group of MPNU (MPNU-d3) and C1-MPNU (C1-MPNU-d3) diminished the SCE-inducing capacity by 20-30% and by 30-40% in DMPNU (DMPNU-d3B). There was no altered SCE activity detected when the phenyl group of MPNU (MPNU-d5) or the 3-methyl group of DMPNU (DMPNU-d3A) was deuterium labeled. No isotope effect was detected in deuterated EPNU derivatives, presumably due to the instability of these compounds. It is surmised that the easier delocalization of the positive charge in the deuterated alkyl diazonium ion causes a diminished reactivity and therefore influences the type and amount of DNA alkylation. Furthermore, the experiments with DMPNU and its derivatives revealed that, in contrast to mono- and disubstituted nitrosoureas, the biological activities of these very stable trisubstituted nitrosoureas are strongly influenced by a serum factor in the culture fluid.
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003903:Deuterium / Q000494:pharmacology*; D005038:Ethylnitrosourea / Q000633:toxicity; D066298:In Vitro Techniques; D008770:Methylnitrosourea / Q000633:toxicity; D009607:Nitrosourea Compounds / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D009607:Nitrosourea Compounds; D008770:Methylnitrosourea; D003903:Deuterium; D005038:Ethylnitrosourea