The overall objective of the proposed project is to elucidate the biological mode of action of N-nitrosamines by: 1) testing unusual model nitrosamines (alpha,-beta-substituted etc.) in vivo for carcinogenicity and in vitro for mutagenicity and oncogenic transformation; (2) Determine potential of nuclear and microsomal enzymes to activate various C-14 labeled nitrosamines of alkylating agents which bind to endogenous (nuclei) and exogenous, (microsomes) DNA; (3) Characterize bound adducts from nuclear and microsomal systems to detect any potential differences; (4) Determine the effect of deuteration of specific sites on various nitrosamines on the formation of major metabolic products.