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Topinka, J. ; Loli, P.* ; Hurbankova, M.* ; Kovacikova, Z. ; Volkovova, K.* ; Wolff, T. ; Oesterle, D. ; Kyrtopoulos, S.A.* ; Georgiadis, P.*

Benzo[a]pyrene-enhanced mutagenesis by man-made mineral fibres in the lung of alpha-lacl transgenic rats.

Mutat. Res. -Fund. Mol. Mech. Mutag. 595, 167-173 (2006)

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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

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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.

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