Evaluation of the effects of cotinine and nicotine-N'-oxides on the development of tumors in rats initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide.
The effects of cotinine and nicotine-N'-oxides on tumor development in F344 rats initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide [(FANFT) CAS: 24554-26-5] were evaluated. When rats were 6 weeks old, FANFT in an agar diet was administered for a 6-week period. Subsequently, cotinine, trans-nicotine-N'-oxide, and a mixture of cis-nicotine-N'-oxide and trans-nicotine-N'-oxide in drinking water were given as promoters in concentrations of 0.1, 0.02, and 0.02%, respectively. These nicotine metabolites were offered ad libitum for 78 weeks. Control groups consisted of rats that received tap water with or without prior administration of FANFT. Cotinine, trans-nicotine-N'-oxide, and the mixture of cis- and trans-nicotine-N'-oxides were neither carcinogens nor promoters of urinary bladder tumors in rats initiated with FANFT. A reduced incidence of urinary bladder tumors was observed in FANFT-pretreated animals that also received a mixture of cis- and trans-nicotine-N'-oxides. FANFT administration increased the incidences of mesothelioma of the peritoneum and thyroid tumors. Tumor formation in the tongue and palate observed in FANFT-treated rats was not affected by administration of these nicotine metabolites. There was, however, a significant increase in the incidence of forestomach tumors in rats that were initiated with FANFT and subsequently received either trans-nicotine-N'-oxide or a mixture of cis- and trans-nicotine-N'-oxides.
D000818:Animals; D001835:Body Weight; D002273:Carcinogens; D003043:Cocarcinogenesis; D003367:Cotinine / Q000633:toxicity*; D003497:Cyclic N-Oxides / Q000633:toxicity*; D004067:Digestive System Neoplasms / Q000139:chemically induced / Q000473:pathology; D004326:Drinking; D004435:Eating; D005200:FANFT / Q000037:antagonists & inhibitors; D008297:Male; D009538:Nicotine / Q000031:analogs & derivatives* / Q000633:toxicity; D011760:Pyrrolidinones / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012907:Smoking; D013237:Stereoisomerism; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000473:pathology
D002273:Carcinogens; D003497:Cyclic N-Oxides; D011760:Pyrrolidinones; C024270:nicotine 1-N-oxide; D009538:Nicotine; D005200:FANFT; D003367:Cotinine