Malignant Tumors in Rats Given Lasiocarpine1

Lasiocarpine was injected i.p. into rats in doses of 7.8 mg/kg body weight (50% lethal dose of 0.1) twice weekly for 4 weeks and once a week for an additional 52 weeks. Of 18 rats that survived, 16 developed tumors between weeks 60 and 76 after the beginning of the experiment. Approximately 61% (11 of 18) developed hepatocellular carcinomas, and 33% (6 of 18) developed well-differentiated squamous cell carcinomas of the skin of the back. These tumors were transplanted successfully through five generations. Other tumors included pulmonary adenoma (in 28%), well-differentiated adenocarcinoma of the small intestine (in two rats), and cholangiocarcinoma and adenomyoma of the ileum (in one rat). It is clear that lasiocarpine is a complete carcinogen capable of inducing a significant number of malignant tumors of the liver and skin of rats. A suitably long experimental interval for administration of the alkaloid (52 weeks) plus a period of observation after the dosing is discontinued (4 to 20 weeks) may be necessary to allow cessation of the antimitotic effect of the alkaloid and to permit expression of its carcinogenicity.