Asbestos exposure affects poly(ADP-ribose) polymerase-1 activity: role in asbestos-induced carcinogenesis

0369504 - BTÚ 2012 RIV GB eng J - Journal Article
Tomasetti, M. - Amati, M. - Nocchi, L. - Saccucci, F. - Strafella, E. - Tarquini, L.M. - Carbonari, D. - Alleva, R. - Borghi, B. - Neužil, Jiří - Bracci, M. - Santarelli, L.
Asbestos exposure affects poly(ADP-ribose) polymerase-1 activity: role in asbestos-induced carcinogenesis.
MUTAGENESIS. Roč. 26, č. 5 (2011), s. 585-591. ISSN 0267-8357
Institutional research plan: CEZ:AV0Z50520701
Keywords : Asbestos exposure * poly(ADP-ribose) polymerase-1 * malignant mesothelioma
Subject RIV: EB - Genetics ; Molecular Biology

Asbestos is known to induce malignant mesothelioma (MM). It is directly genotoxic by inducing DNA strand breaks. Poly(ADP-ribose) polymerase-1 (PARP1) is a protein with a function as a DNA damage sensor. To determine whether PARP1 is involved in asbestos-induced carcinogenesis, PARP1 expression and activity as well as DNA damage and repair were evaluated in circulating cells of asbestos-exposed subjects, MM patients and controls. Accumulation of the pre-mutagenic 8-hydroxy-2'-deoxyguanosine and elevated PARP1 expression were found both in asbestos-exposed subjects and MM patients. Although PARP1 was highly expressed, its activity was relatively low in circulating cells as well as in MM biopsies. Low DNA repair efficiency was observed in lymphocytes from MM patients. To mimic PARP1 dysfunction, PARP1 expression and activity were induced in immortalised mesothelial cells by their exposure to asbestos in the presence of a PARP1 inhibitor, which resulted in transformation of the cells.
Permanent Link: http://hdl.handle.net/11104/0203552