Preliminary investigation into the effect of fulvine on rat and human chromosomes - abstract

ABSTRACT

Some pyrrolizidine alkaloids have been shown to have nuclear toxicity in vitro. Fulvine was therefore investigated for its effect on mitotic chromosomes in the rat and in man. In vitro studies were performed on rat fibroblasts and human and rat peripheral blood cultures. In vivo studies were performed by injecting mature rats subcutaneously with 0.08mg/gm body weight in fulvine. Control animals received the identical dilutant. Blood cultures were established 24 and 48 hours, and 8 days later. Nine children with histologically proven veno-occlusive disease (VOD) and eight controls were studied by 48-hour blood cultures, for changes in chromosome number and morphology. The in vitro studies were negative. In vivo studies in rats showed marked mitotic depression at 24 and 48 hours. On the seventh day, breaks, gaps exchanges and rearrangements were seen in 24 percent of cells. VOD was found in 5 rats. Of the children, three sibs, and two others showed similar abnormalities marked in the former and less so in the latter. These findings are very suggestive of induction of chromosome abnormalities by fulvine or by VOD. The frequency of these changes may be related to dosage levels, intervals between ingestion and examination, or to familial reactions to the drug (AU)