The nicotine-derived /V-nitrosamine 4-(methylnitrosamino)-l-(3-pyri-(hl)-l-hiilaiHiiH ' (NNK) is abundant in smokeless tobacco and tobacco smoke and is hepatocarcinogenic in F344 rats. We have investigated how vitamin A modulates sister chromatid exchanges and DNA single-strand breaks induced by NNK. In V79 cells, vitamin A at concentrations ranging from 34.9 to 139.6 n\i inhibited sister chromatid exchange frequencies induced by 20 mivi NNK activated by primary rat hepatocytes. Sister chromatid exchanges were inhibited by 24, 44, and 55 % when cells were cotreated with 34.9, 69.8, and 139.6 MMvitamin A, respectively. DNA single-strand breaks induced by NNK in rat hepatocytes were also inhibited by vitamin A. After 9 h of elution, DNA single-strand breaks induced by 1, 5, and 10 HIMNNK were inhibited by 13, 5, and 3.5 % in the presence of 69.8 Â¿IMvitamin A, respectively. This protective effect by vitamin A was associated with a reduction of a-carbon hydroxylation
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