Mutagenesis by asbestos in the lung of lambda-lacI transgenic rats.
In order to get more insight into the mechanism of asbestos-related lung cancer, the mutagenic potential of asbestos was examined in vivo in rat lung. Groups of five transgenic lambda-lacI (Big Blue) rats were intratracheally instilled with single doses of 1 or 2mg, or with four weekly doses of 2mg, per animal of the amosite asbestos. Sixteen weeks after instillation, the mutation frequency was found to be increased in lung DNA by 2-fold at doses of 2 mg (P = 0.035) and of 4 x 2 mg (P = 0.007) amosite. No significant changes were observed after 4 weeks of exposure. In separate experiments, wild-type F344 rats were treated by the same regimen as described above and markers of inflammation, genotoxicity, cell proliferation and lung tissue damage were analysed. Our results indicate a weak but persistent inflammation and cell proliferation which possibly plays a major role in the observed mutagenic effect.
Topinka
J
J
GSF-National Research Center for Environment and Health, Institute of Toxicology, Neuherberg, Germany. jtopinka@biomed.cas.cz
Loli
P
P
Georgiadis
P
P
Dusinská
M
M
Hurbánková
M
M
Kováciková
Z
Z
Volkovová
K
K
Kazimírová
A
A
Barancoková
M
M
Tatrai
E
E
Oesterle
D
D
Wolff
T
T
Kyrtopoulos
S A
SA
D000818:Animals; D030801:Animals, Genetically Modified; D001194:Asbestos / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008315:Malondialdehyde / Q000032:analysis; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics
D009153:Mutagens; D012097:Repressor Proteins; D001194:Asbestos; D008315:Malondialdehyde