The nitrosated bile acid conjugate N-nitrosoglycocholic acid reacts with DNA to give rise to several adducts including O6-carboxymethylguanine and, unexpectedly, O6-methylguanine (6-MG). O6-MG is well established as a toxic and promutagenic lesion and is a substrate for the DNA repair protein O6-alkylguanine-DNA-alkyltransferase. In contrast, O6-carboxymethylguanine is not repaired by this protein. Similar results have been obtained for other nitrosated glycine derivatives, which suggests that O6-MG, which has been observed in DNA from human gastrointestinal tissues, may be derived from intragastric nitrosation of glycine or related compounds.

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This work was supported by the Medical Research Council and the Cancer Research Campaign.

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