CHARACTERIZATION OF HEPATIC DNA DAMAGE INDUCED IN RATS BY THE PYRROLIZIDINE ALKALOID MONOCROTALINE

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (4) , 1505-1509
Abstract
Hepatic DNA damage induced by the pyrrolizidine alkaloid monocrotaline was evaluated following i.p. administration to adult male Sprague-Dawley rats. Animals were treated with various doses ranging upward from 5 mg/kg, and hepatic nuclei were isolated 4 h later. Hepatic nuclei were used as the DNA source in all experiments. DNA source in all experiments. DNA damage was characterized by the alkaline elution technique. A mixture of DNA-DNA interstrand cross-links and DNA-protein cross-links was induced. Following an injection of monocrotaline, 30 mg/kg i.p., DNA-DNA interstrand cross-linking reached a maximum within 12 h or less and thereafter decreased over a protracted period of time. By 96 h postadministration, the calculated cross-linking factor was no longer statistically different from zero. No evidence for the induction of DNA single-strand breaks was observed, although the presence of small numbers of DNA single-strand breaks could have been masked by the overwhelming predominance of DNA cross-links. These DNA cross-links may be related to the hepatocarcinogenic, hepatotoxic, and/or antimitotic effects of monocrotaline.