Characterization of hepatic DNA damage induced in rats by the pyrrolizidine alkaloid monocrotaline
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.
- Research Organization:
- Department of Pharmacology, University of Arizona, Health Sciences Center, Tucson
- OSTI ID:
- 7188790
- Journal Information:
- Cancer Res.; (United States), Vol. 44:4
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ALKALOIDS
BIOLOGICAL EFFECTS
DNA
CROSS-LINKING
LIVER
RATS
ANIMALS
BODY
CHEMICAL REACTIONS
DIGESTIVE SYSTEM
GLANDS
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
POLYMERIZATION
RODENTS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)