Asbestos is known to induce malignant mesothelioma (MM) and other 
asbestos-related diseases. It is directly genotoxic by inducing DNA strand 
breaks and cytotoxic by promoting apoptosis in lung target cells. 
Poly(ADP-ribose) polymerase-1 (PARP1) is a nuclear zinc-finger 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 age-matched controls. PARP1 expression and activity 
were also evaluated in pleural biopsies of MM patients and compared with normal 
tissue. 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. 
Low DNA repair efficiency was observed in lymphocytes from MM patients. High 
expression of PARP1 associated with low PARP activity was also found in MM 
biopsies. 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. We propose 
that exposure to asbestos inhibits the PARP1 activity possibly resulting in 
higher DNA instability, thus causing malignant transformation.