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Genotoxicity of a Variety of Pyrrolizidine Alkaloids in the Hepatocyte Primary Culture-DNA Repair Test Using Rat, Mouse, and Hamster Hepatocytes

Department of Pathology, Gifu University School of Medicine, Gifu 500, Japan [H. M., S. S., N. Y.]; School of Pharmaceutical Science, Kitasato University, Shirokane, Minato-ku, Tokyo 108, Japan [Y. A., T. F.]; and Naylor Dana Institute, American Health Foundation, Valhalla, New York 10595 [G. M. W.]

Seventeen pyrrolizidine alkaloids were studied with the hepatocyte primary culture-DNA repair test using rat hepatocytes. DNA repair synthesis was elicited by 15 alkaloids, including 11 of unknown carcinogenicity, i.e., senecionine, seneciphylline, jacobine, epoxyseneciphylline, senecicannabine, acetylfukinotoxin, syneilesine, dihydroclivorine, ligularidine, neoligularidine, and ligularizine. The positive results with these alkaloids of unknown carcinogenicity suggest that they are possibly genotoxic carcinogens. The two pyrrolizidine alkaloids that did not elicit DNA repair were retronecine which lacks a necic acid component and ligularinine which lacks the unsaturated double bond at the 1,2-position of the pyrrolizidine ring. Five pyrrolizidine alkaloids, retronecine, monocrotaline, seneciphylline, senkirkine, and clivorine, were also tested in the DNA repair test with hamster or mouse hepatocytes. These alkaloids, except retronecine, showed a positive response in the test with hamster hepatocytes, but in the test with mouse hepatocytes clivorine in addition to retronecine was also negative. The results indicate a species difference in liver bioactivation of pyrrolizidine alkaloids, implying that there could be species differences in their carcinogenic activities.

¹ To whom requests for reprints should be addressed.

Received 1/14/85. Accepted 3/ 8/85.

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