Induction of Liver Tumors in F344 Rats by Crotonaldehyde

The tumorigenic activities in F344 rats of crotonaldehyde, a representative α,β-unsaturated carbonyl compound, and N-nitro-sopyrrolidine, which could produce crotonaldehyde upon metabolism, were compared. Groups of rats were treated with either crotonaldehyde (0.6 mM or 6.0 mM) or N-nitrosopyrrolidine (0.6 mM) in their drinking water for 113 or 84 weeks, respectively. At the 0.6 mM dose, crotonaldehyde induced neoplastic lesions of the liver in 9 of 27 rats; 2 rats had hepatocellular carcinomas, and 9 rats had neoplastic nodules. It also caused altered liver cell foci in 23 of 27 rats. The incidences of tumors and foci were significantly higher than those of the control group. N-Nitroso-pyrrolidine induced hepatocellular carcinomas in 20 of 23 rats, liver neoplastic nodules in 16 of 23 rats, and altered liver cell foci in 23 of 23 rats. Thus, crotonaldehyde appears to be a weaker tumorigen than N-nitrosopyrrolidine. At the 6.0 mM dose, crotonaldehyde treatment caused moderate to severe liver damage in 10 of 23 rats. No preneoplastic or neoplastic lesions were observed in these rats. The remaining 13 rats of this group developed altered liver cell foci. The tumorigenicity of crotonaldehyde suggests that α,β-unsaturated carbonyl compounds, which are ubiquitous in the human environment and can be formed endogenously, may be an important class of potential carcinogens. copyright.