Benzo[a]pyrene-enhanced mutagenesis by man-made mineral fibres in the lung of lamda-lacI transgenic rats.
In an attempt to examine the interaction of man-made mineral fibres with benzo[a]pyrene (B[a]P), homozygous X-lacI transgenic F344 rats were intratracheally treated with rock (stone) wool RWI 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.
Topinka
J
J
GSF-National Research Centerfor Environment and Health, Institute of Toxicology, Ingolstaedter Landstrasse 1, D-85764 Neuherberg, Germany. jtopinka@biomed.cas.cz
Loli
P
P
Hurbáková
M
M
Kováciková
Z
Z
Volkovová
K
K
Wolff
T
T
Oesterle
D
D
Kyrtopoulos
S A
SA
Georgiadis
P
P
D000818:Animals; D030801:Animals, Genetically Modified; D001194:Asbestos / Q000633:toxicity; D010582:Bacteriophage lambda / Q000235:genetics*; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D018736:DNA Adducts / Q000235:genetics; D007763:Lac Operon / Q000235:genetics*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D019016:Mineral Fibers / Q000009:adverse effects*; D016296:Mutagenesis / Q000187:drug effects* / Q000235:genetics; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress; D051381:Rats; D011916:Rats, Inbred F344
D018736:DNA Adducts; D019016:Mineral Fibers; D001194:Asbestos; D001564:Benzo(a)pyrene; D008315:Malondialdehyde