Synthesis of poly(ADP-ribose) in asbestos treated rat pleural mesothelial cells in culture.
To investigate the origin of DNA repair in rat pleural mesothelial cells (RPMC) exposed to asbestos fibers, poly(ADP-ribose) polymerase (PARP) activity was measured in the asbestos-treated cells. As bleomycin has been shown to activate poly(ADP-ribose) synthesis in several cell systems, the response to bleomycin with regard to PARP assay was first investigated. Bleomycin produced a dose-dependent increase of poly(ADP-ribose) synthesis in RPMC. Likewise both chrysotile and crocidolite fibers produced a concentration-dependent PARP activation indicating that the formation of DNA strand breaks is one type of damage produced by asbestos in RPMC. Enhancement of DNA repair, assessed by the measurement of [3H] methylthymidine incorporation in growth arrested cells, was not detectable in the presence of 3-methoxybenzamide (3-MBA), a PARP inhibitor, confirming a relation between PARP activation and DNA repair. The participation of DNA breakage in asbestos toxicity on RPMC was determined by the colorimetric 3-4(5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. There was no relationship between DNA breakage and cytotoxicity since the use of PARP inhibitors did not change cell viability. These results indicate that asbestos produce DNA damage that is repaired in RPMC.
Dong
H Y
HY
Laboratory of Environmental Cellular and Molecular Pathology, Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor, Institut Mondor de Médecine Moléculaire, Faculté de Médecine, Créteil, France.
Buard
A
A
Lévy
F
F
Renier
A
A
Laval
F
F
Jaurand
M C
MC
D000818:Animals; D001194:Asbestos / Q000633:toxicity*; D017638:Asbestos, Crocidolite / Q000633:toxicity; D017632:Asbestos, Serpentine / Q000633:toxicity; D001549:Benzamides / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium; D009153:Mutagens / Q000633:toxicity*; D009536:Niacinamide / Q000494:pharmacology; D010994:Pleura / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats
D017632:Asbestos, Serpentine; D001549:Benzamides; D004791:Enzyme Inhibitors; D009153:Mutagens; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D001761:Bleomycin; D017638:Asbestos, Crocidolite; D001194:Asbestos; D009536:Niacinamide; D011064:Poly Adenosine Diphosphate Ribose; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases; C025159:3-methoxybenzamide