Benzo(a)pyrene-enhanced mutagenesis by man-made mineral fibres in the lung of λ-lacI transgenic rats

In an attempt to examine the interaction of man-made mineral fibres with benzo[ a]pyrene (B[a]P), homozygous λ-lacI transgenic F344 rats were intratracheally treated with rock (stone) wool RW1 and glass wool MMVF 10 fibres together with B[ a]P. To analyze the induction of gene mutations by fibres and B[ a]P in lung, single doses of 1 and 2 mg fibres/animal or multiple doses of 2 mg fibres/animal were administered weekly on 4 consecutive weeks (total dose 8 mg/animal). B[ a]P (10 mg/animal) was administered either simultaneously with fibres (for single dose treatment with fibres) or together with the last fiber treatment (for multiple dose treatment with fibres). Animals were scarified 4 weeks after the last treatment. Benzo[ a]pyrene administered simultaneously with RW1 fibres exhibited a strong synergistic effect on mutagenicity, the observed mutant frequency (MF) being more than three-fold higher than the net sum of the MF induced after separate administration of both agents. Our data suggest that DNA adducts induced by simultaneous B[a]P and fiber treatment lead to a strong increase in mutatant frequencies. © 2005 Elsevier B.V. All rights reserved.