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Nitrosated Glycine Derivatives as a Potential Source of O⁶-Methylguanine in DNA¹

MRC Toxicology Unit, Hodgkin Building, University of Leicester, P. O. Box 138, Lancaster Road, Leicester LE1 9HN [D. E. G. S.], and CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester M20 9BX [G. P. M.], United Kingdom

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.

¹ This work was supported by the Medical Research Council and the Cancer Research Campaign.

² To whom requests for reprints should be addressed, at the MRC Toxicology Unit, Hodgkin Building, University of Leicester, P. O. Box 138, Lancaster Road, Leicester LE1 9HN, UK.

Received 10/10/96. Accepted 12/18/96.

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