Metabolism of dimethylnitrosamine and subsequent removal of O6-methylguanine from DNA by isolated rat hepatocytes

Diane R. Umbenhauer, Anthony E. Pegg

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Abstract

Freshly prepared isolated hepatocytes were shown to metabolize dimethylnitrosamine producing an alkylating agent which reacted with cellular DNA giving rise to 7-methylguanine and O6-methylguanine. Alkylation of DNA was prevented by aminoacetonitrile and was proportional to the dimethylnitrosamine concentration over the range of 1-90 μM. Isolated hepatocytes were able to catalyze the removal of O6-methylguanine from their DNA. After formation of this product by reaction with N-methyl-N-nitrosourea or dimethylnitrosamine to give extents of alkylation in the range of 0.1-15.0 μmol O6-methylguanine per mole of guanine in DNA, the loss produced in 3 h incubation was comparable to that seen in vivo from liver DNA alkylated to the same extent. The isolated hepatocytes therefore, provide a useful system in which factors influencing O6-methylguanine persistence in DNA can be studied.

Original languageEnglish (US)
Pages (from-to)229-238
Number of pages10
JournalChemico-Biological Interactions
Volume33
Issue number2-3
DOIs
Publication statusPublished - Jan 1981

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All Science Journal Classification (ASJC) codes

  • Toxicology

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