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.
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and nitrosonornicotine (NNN) were administered to lacZ mice (MutaMouse) 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 approximately 6 to 40 mutants per 10(-5) plaque forming units This corresponds to approximately 2-13 times the background levels. A somewhat different pattern was observed with NNN, where the order was liver > esophagus oral tissue approximately 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 approximately 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 approximately 15-50% in liver, lung, pooled oral tissue and esophagus.
von Pressentin
M M
MM
Division of Basic Sciences/Biochemistry, New York University Dental Center, 345 East 24th Street, New York, NY 10100, USA.
Chen
M
M
Guttenplan
J B
JB
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004947:Esophagus / Q000187:drug effects; D005260:Female; D007763:Lac Operon / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008168:Lung / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009055:Mouth / Q000187:drug effects; D016296:Mutagenesis / Q000187:drug effects*; D009296:Nasal Cavity / Q000187:drug effects; D009602:Nitrosamines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009928:Organ Specificity; D013662:Tea; D014059:Tongue / Q000187:drug effects
D016587:Antimutagenic Agents; D002273:Carcinogens; D009602:Nitrosamines; D013662:Tea; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C008655:N'-nitrosonornicotine