INDUCTIONS OF OXIDATIVE DNA-DAMAGE AND MESOTHELIOMA BY CROCIDOLITE, WITH SPECIAL REFERENCE TO THE PRESENCE OF IRON INSIDE AND OUTSIDE OF ASBESTOS FIBER

Inductions of oxidative DNA damage (oh(8)dG) in vitro and peritoneal m esothelioma in rats (F344, female) were compared between crocidolite ( CR) and de-ironized crocidolite [DCR, washed by HCl and ethylenediamin e tetraacetic acid (EDTA)] to verify the hypothesis that reactive oxyg en species contribute to carcinogenesis, focusing on the role of iron present inside or outside of the CR. The yield of oh(8)dG was 14.6 oh( 8)dG/10(5)dG in CR and 30.2 in DCR under simple incubation with DNA. I n the incubation systems added several chemicals and H2O2, DCR induced higher levels of oh(8)dG than CR. Especially, the addition of Fe2O3 a nd H2O2 to DCR increased oh(8)dG in DNA depending on the Fe2O3 concent ration, however, this tendency was not observed in the same system of CR. Surprisingly, 7 out of 10 rats died within 2 days after the inject ion of 10 mg of Fe2O3 following the DCR injection (5 mg/rat), showing necroses of hepatocytes from the surface of each lobe where CR and Fe2 O3 particles had been deposited together. There was no death in other groups of rats. One year after the i.p. injection of CR (5 mg/rat, sin gle injection), mesotheliomas were found in all rats administered DCR and Fe2O3 (2 mg/rat, once a week, for 35 weeks), in 4 rats of DCR alon e (n = 10), in 5 rats of CR alone (n = 10) and in none of the rats adm inistered Fe2O3 alone (n = 10). Therefore, present results indicate th at the induction of oxidative DNA damage changed even when the same ty pe of asbestos was washed by chemical treatment, and Fe2O3 promoted th e development of mesothelioma which was induced by DCR.