title: Characterization of hepatic DNA damage induced in rats by the pyrrolizidine alkaloid monocrotaline.
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 hr later. Hepatic nuclei were used as the 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 hr or less and thereafter decreased over a protracted period of time. By 96 hr 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.
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000528:radiation effects; D004261:DNA Replication / Q000187:drug effects* / Q000528:radiation effects; D004277:DNA, Single-Stranded / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007939:Leukemia L1210 / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016686:Monocrotaline; D010947:Plants, Toxic; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012674:Senecio
chemical_list: D004277:DNA, Single-Stranded; D011763:Pyrrolizidine Alkaloids; D016686:Monocrotaline