Reactive intermediates from nitrosamines.

M C Archer

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PubMed · 6178268

Reactive intermediates from nitrosamines.

M C Archer

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Abstract

Metabolism of N-nitrosodi-n-propylamine by isolated rat liver fractions yielded both n-propanol and isopropanol, providing evidence for a reaction sequence, initiated by formation of the alpha-hydroxynitrosamine, that leads to formation of carbonium ions. Administration of N-nitrosodi-n-propylamine to rats led to formation of 7-n-propylguanine but not 7-isopropylguanine in hepatic DNA, showing that in the intact cell, the reaction sequence is intercepted by nucleophilic sites in DNA before a carbocation is formed. Alkylation of DNA therefore appears to occur primarily by a bimolecular reaction not involving free alkyl cations. N-nitrosodi-n-propylamine is also oxidized by rat liver microsomes by two consecutive beta-oxidation reactions to yield N-nitroso-2-oxopropylpropylamine. The latter agent leads to production of 7-methylguanine and O6-methylguanine in liver DNA following its administration to rats. The chemical nature of the ultimate methylating agent is unclear.

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Animals Biotransformation Carcinogens DNA Liver Microsomes, Liver Nitrosamines RNA Rats Structure-Activity Relationship Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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M C Archer. 1981. Reactive intermediates from nitrosamines.. https://pubmed.ncbi.nlm.nih.gov/6178268/

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