Comparative carcinogenicity and metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N'-nitrosonornicotine in Syrian golden hamsters.
The tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) were tested for carcinogenic activity in Syrian golden hamsters. In Assay A, 30 hamsters were each given 19 s.c. injections of 0.048 mmol of NNK or NNN. In Assay B, 20 hamsters each received 75 s.c. injections of 0.012 mmol of NNK or NNN. Among the NNK-treated hamsters in Assay A, three developed carcinomas of the nasal cavity, and 19 had adenomas and/or adenocarcinomas of the lung. In the NNN group, one hamster developed a lung adenoma, and five had tracheal papillomas. In Assay B, 11 of the NNK-treated hamsters developed carcinomas of the nasal cavity, 16 had lung adenomas and/or adenocarcinomas, and seven had tracheal papillomas; in the NNN group, we recorded only one hamster with a lung adenoma and one with a tracheal papilloma. These findings in the Syrian golden hamster confirm that NNK is a more powerful carcinogen than NNN, as was shown previously in assays with rats and mice. In metabolism studies, 96 to 98% of the radioactivity of the injected [1-14C]NNK was recovered in the urine, 4% was recovered in the feces, and less than 0.5% was recovered as exhaled 14CO2. The corresponding distribution for [2'-14C]NNN was 62 to 78% in urine, 10% in feces, and less than 0.5% in respiratory 14CO2. The levels of binding of [1-14C]NNK and [2'-14C]NNN to the trichloroacetic acid-insoluble fractions were highest in liver, lung, kidney, and adrenals. The urinary metabolites of NNK and NNN resulted from alpha-hydroxylation, from N-oxidation of NNN to N'-nitrosonornicotine-1-N-oxide, and from reduction of NNK to 4-(methylnitrosamino)-1-(3-pyridyl)butan-1-ol.
D000818:Animals; D002273:Carcinogens; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D005243:Feces / Q000032:analysis; D005260:Female; D007279:Injections, Subcutaneous; D008175:Lung Neoplasms / Q000139:chemically induced; D008297:Male; D008647:Mesocricetus; D009296:Nasal Cavity; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009538:Nicotine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity / Q000652:urine; D009602:Nitrosamines / Q000378:metabolism / Q000633:toxicity* / Q000652:urine; D009669:Nose Neoplasms / Q000139:chemically induced; D010947:Plants, Toxic; D011725:Pyridines / Q000378:metabolism / Q000633:toxicity / Q000652:urine; D014026:Nicotiana
D002273:Carcinogens; D009602:Nitrosamines; D011725:Pyridines; D009538:Nicotine; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C008655:N'-nitrosonornicotine