Assays for metabolic alpha-hydroxylation of N'-nitrosonornicotine and N-nitrosopyrrolidine and the influence of modifying factors.

C. B. Chen, S. S. Hecht, G. D. McCoy, D. Hoffmann

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

High-pressure liquid chromatographic methods were developed to study microsomal alpha-hydroxylation, which is likely to be an activation mechanism for N-nitrosopyrrolidine (NPYR) and N'-nitrosonornicotine (NNN). The effects of ethanol, phenobarbital and 3-methylcholanthrene pretreatment on the alpha-hydroxylation of NPYR and NNN were determined using F-344 rats and Syrian golden hamsters. In the rat, 3-methylcholanthrene pretreatment decreased the rates of alpha-hydroxylation of NPYR and 5'-hydroxylation of NNN, but increased the rate of 2'-hydroxylation of NNN. Phenobarbital pretreatment of rats did not markedly affect rates of alpha-hydroxylation of NPYR or NNN. In the hamster, 3-methylcholanthrene pretreatment increased the rate of alpha-hydroxylation of NPYR, but did not affect the rates of alpha-hydroxylation of NNN. Phenobarbital or ethanol pretreatment of hamsters resulted in increased rates of alpha-hydroxylation of NPYR and 5'-hydroxylation of NNN. The induction of alpha-hydroxylation of NNN and NPYR by ethanol suggests that these nitrosamines may be more carcinogenic in alcohol-treated animals.

Original languageEnglish (US)
Pages (from-to)349-359
Number of pages11
JournalIARC scientific publications
Issue number31
StatePublished - 1980

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