DNA damage in tissues of rat treated with potassium canrenoate.
Potassium canrenoate (PC), a competitive aldosterone antagonist previously found to increase tumor incidence in rats and to produce genotoxic effects in in vitro systems, was examined in rats to acquire information on its genotoxic activity in vivo. Intragastric administration of 1/2 LD50 produced, as revealed by the Comet assay, a modest but statistically significant increase in the frequency of DNA lesions in liver but not in thyroid and bone marrow of male rats, and in thyroid and bone marrow but not in liver of female rats. In contrast with the frankly positive responses observed in primary cultures of rat hepatocytes (Martelli et al., Mutagenesis 14 (1999) 463-472) any evidence of DNA repair and micronuclei formation was absent in liver of rats treated with 1/2 LD50, and initiation of enzyme-altered liver preneoplastic lesions did not occur in the liver of rats given 100 mg/kg PC once a week for 6 successive weeks. A high and dose-dependent frequency of DNA lesions was found to occur in testes and ovaries of rats given single doses ranging from 1/8 to 1/2 LD50.
Martelli
Antonietta
A
Department of Internal Medicine, Division of Clinical Pharmacology and Toxicology, University of Genoa, Tossicologia Clinica, Viale Benedetto XV 2, I-16132, Genoa, Italy.
Carrozzino
Roberto
R
Mattioli
Francesca
F
Bucci
Giovanna
G
Lamarino
Giorgia
G
Brambilla
Giovanni
G
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002191:Canrenoic Acid / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage; D053938:DNA Fragmentation; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D022781:Hepatocytes / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D015162:Micronucleus Tests; D000451:Mineralocorticoid Receptor Antagonists / Q000633:toxicity*; D010053:Ovary / Q000187:drug effects; D051381:Rats; D013737:Testis / Q000187:drug effects; D013961:Thyroid Gland / Q000187:drug effects
D000451:Mineralocorticoid Receptor Antagonists; D002191:Canrenoic Acid