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Nitrosated glycine derivatives as a potential source of O6-methylguanine in DNA
1MRC Toxicology Unit, Hodgkin Building, University of Leicester, United Kingdom.
Cancer Research
|February 1, 1997
Abstract:
The nitrosated bile acid conjugate N-nitrosoglycocholic acid reacts with DNA to give, rise to several adducts including O6-carboxymethylguanine and, unexpectedly, O6-methylguanine (O6-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.