Journal Article

Mutagenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and <i>N</i>-nitrosonornicotine in <i>lacZ</i> upper aerodigestive tissue and liver and inhibition by green tea

Marcia d.M.von Pressentin, Michael Chen and Joseph B. Guttenplan

in Carcinogenesis

Volume 22, issue 1, pages 203-206
Published in print January 2001 | ISSN: 0143-3334
Published online January 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.1.203
Mutagenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N-nitrosonornicotine in lacZ upper aerodigestive tissue and liver and inhibition by green tea

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4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and nitrosonornicotine (NNN) were administered to lacZ mice (Muta™Mouse) at equal concentrations in drinking water (2 weeks at 0.1 followed by 2 weeks at 0.2 mg/ml) over a 4 week period, for a total estimated dose of 615 mg/kg) and mutagenesis in a number of organs was measured. For mutagenesis induced by NNK the potency order was: liver > lung> pooled oral tissues kidney > esophagus > tongue. The mutant fraction varied from ~6 to 40 mutants per 10–5 plaque forming units This corresponds to ~2–13 times the background levels. A somewhat different pattern was observed with NNN, where the order was: liver > esophagus oral tissue ≈ tongue > lung > kidney. The potency of NNK was about twice that of NNN in liver and lung, but somewhat less in aerodigestive tract tissue. When compared with results previously obtained for a similar administered dose of benzo[a]pyrene, NNK was ~10–100% as mutagenic in the corresponding organs. Reported target organs for carcinogenesis by NNN and NNK in rodents were targets for mutagenesis, but mutagenesis was also observed at other sites, suggesting that these sites are initiated. The effect of green tea consumption on mutagenesis by NNK was also investigated. Green tea reduced mutagenesis by ~15–50% in liver, lung, pooled oral tissue and esophagus.

Keywords: BaP, benzo[a]pyrene; MF, mutant fraction; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; NNN, nitrosonornicotine; TSN, tobacco-specific nitrosamines.

Journal Article.  3149 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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