title: Quantitative structure-activity relationship of the mutagenicity of substituted N-nitroso-N-benzylmethylamines: possible implications for carcinogenicity.
abstract: The relative mutagenicities of substituted N-nitroso-N-benzylmethylamines have been reexamined from a quantitative structure-activity relationship point of view. Most of the compounds were mutagenic toward Salmonella typhimurium TA 1535 with Aroclor-induced male hamster liver S9 activation. The dose-response data were subjected to a multiple linear regression equation calculated in a stepwise manner, which found that the differences in mutagenicities could be explained primarily by differences in the three-bond path molecular connectivity index, with smaller contributions from sigma and pi. Moreover, a polynomial regression analysis showed that the maximum mutagenicity could be explained by an optimal amount of electron withdrawal by the substituent which would cause a weakening, or activation, of the methylene C-H bond. The possible relevance of these observations to carcinogenesis is discussed.
mesh_terms: D000818:Animals; D002273:Carcinogens; D055598:Chemical Phenomena; D002621:Chemistry; D006224:Cricetinae; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D002273:Carcinogens; D009153:Mutagens; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine