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.


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

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