The effects of fulvine on human and rat mitotic chromosomes

ABSTRACT

With increasing interest in mutagenicity an array of agents such as chemicals and drugs are being defined as chromosome damaging agents. The activities of these agents were reviewed. An intensive investigation of the mutagenic potential of fulvine was undertaken for three reasons. 1. Fulvine is still widely consumed in Jamaica as a herbal remedy which causes a well defined pathological condition - veno - occlusive disease of the liver (VOD). 2. Fulvine was found to cause chromosome damage in previous screening experiments. 3. Fulvine is a member of the pyrrolizidine group of alkaloids which are known to have mutagenic effects. The mutagenic activities were investigated by in vivo studies in children who have recovered from VOD and experimentally in rats. Serial examination of 3 members of a family recently recovered showed a decline of the percentage of cells with damage to normal over a five month period. No abnormalities were detected in 7 recovered children. Fulvine was administered to rats at varying dosages of 0.08 mg/gm, 0.04 mg/gm, 0.02 mg/gm, 0.01 mg/gm, and repeated administrations of 0.04 mg/gm body weight. Chromosomal abnormalities were produced which included gaps, breaks, bivalent and quadriradial configurations, ring chromosomes, dicentrics, abnormal metacentrics and submetacentrics, chromatic exchanges. Tetraploidy was rarely detected. The abnormalities were comparable in type to those seen in human VOD. At all dosages exchanges predominated over other types of abnormalities. Abnormalities were induced within 48 hours after fulvine administration at a threshold dosage of 0.02 mg/gm. Mitotic inhibition and liver damage were more marked in 12 weanling rats treated with doses of 0.08 mg/gm body weight of fulvine. The model for investigation of fulvine as a mutagenic agent was evaluated (AU)