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

J Natl Cancer Inst. 1985 Dec;75(6):1075-81.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Weight
  • Carcinogens*
  • Cocarcinogenesis
  • Cotinine / toxicity*
  • Cyclic N-Oxides / toxicity*
  • Digestive System Neoplasms / chemically induced
  • Digestive System Neoplasms / pathology
  • Drinking
  • Eating
  • FANFT / antagonists & inhibitors
  • Male
  • Nicotine / analogs & derivatives*
  • Nicotine / toxicity
  • Pyrrolidinones / toxicity*
  • Rats
  • Rats, Inbred F344
  • Smoking
  • Stereoisomerism
  • Urinary Bladder Neoplasms / chemically induced*
  • Urinary Bladder Neoplasms / pathology


  • Carcinogens
  • Cyclic N-Oxides
  • Pyrrolidinones
  • nicotine 1-N-oxide
  • Nicotine
  • Cotinine