No abstract

No abstract

We used transgenic mice carrying the laI reporter gene to study the mutagenesis potential of asbestos crocidolite. The animals were exposed by nose-ondy inhalation to an aerosol containg 5.75 mg/m3 crocidolite dust for 6 hr/day and 5 consecutive days. After 1, 4, and 12 weeks, we examined four end points: the cytology of bronchoalveolar lavage, the lung load of crocidolite, the hydrophobic DNA adducts, and the mutations in the lacIreporter gene. Twelve weeks after exposure, nearly 10% of the inhaled fibers remained in the lung (227 ± 103 ng/mg lung). There was evidence of a typical inflammatory response consisting of multinudeate macrophages at weeks 4 and 12, whereas immediately after the exposure, we observed numerous polymorphonudear neutrophils. The mutant frequency significatively increased during the fourth week after the exposure: 13.5 x 10-5 in the exposed group versus 6.9 x 10-5 in the control group. The induction factor, defined by the ratio of checked mutants of exposed mice to checke mutants of control mice, was 1.96. The mutation spectrum of control lung DNA and exposed lung DNA was similar, suggesting the possible involvement ofa DNA repair decrease in crocidolite-treated animals. We used the 32p-posdabeling method and did not detect any increase of either 5 mC or bulky adduct in treated mice. This is the first study that demonstrates asbestos mutagenicity in vivo after a nose-only inhalation.

No abstract

No abstract