Characterization of hepatic DNA damage induced in rats by the pyrrolizidine alkaloid monocrotaline

Journal Article · Sun Apr 01 00:00:00 EST 1984 · Cancer Res.; (United States)

OSTI ID:7188790

Petry, T W; Bowden, G T; Huxtable, R J; Sipes, I G

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

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
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)