On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo[a]pyrene: II. Tissue specificity studies using comet assay.
Epidemiological data seem to be equivocal on the probable increase in cancer incidence in populations exposed to asbestos-fibre contaminated drinking water. Although animal experiments failed to demonstrate carcinogenicity of oral asbestos exposure, the large surface area of the fibres, however, creates the possibility of cogenotoxic action with adsorbed water-borne organics. In our animal model, rats were gavaged with untreated UICC crocidolite and anthophyllite fibres and fibres that had been allowed to adsorb benzo[a]pyrene molecules from aqueous solutions. Peritoneal macrophages and intestine, parietal peritoneum and omentum samples were obtained from the animals after 24 h. The alkaline single-cell microgel electrophoresis assay (comet assay) was performed on cells isolated from the solid tissues. Tail moment was applied as a basis of evaluation following image analysis. Our results indicate high levels of DNA strand breaks in the cells prepared from the omentum and intestine. We could also demonstrate a significant potentiating effect of the adsorbed carcinogen on the induction of DNA damage in the omentum. The parietal peritoneum and macrophages were not involved in the early genotoxic alterations under study. Our results support the molecular model of asbestos cocarcinogenesis, including both asbestos-induced deletions and mutations caused by a mutagen carried by the same fibres.
Varga
C
C
Department of Hygiene & Epidemiology, University Medical School, Debrecen, Hungary. csvarga@jaguar.dote.hu
Horváth
G
G
Timbrell
V
V
D000818:Animals; D017636:Asbestos, Amphibole / Q000633:toxicity*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D003043:Cocarcinogenesis; D004247:DNA / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D004195:Disease Models, Animal; D004357:Drug Synergism; D004586:Electrophoresis / Q000379:methods; D005260:Female; D006863:Hydrogen-Ion Concentration; D007422:Intestines / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects; D009852:Omentum; D009928:Organ Specificity; D010537:Peritoneum / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D017636:Asbestos, Amphibole; D002273:Carcinogens; D001564:Benzo(a)pyrene; D004247:DNA