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Visualization and Quantitative Analysis of Genotoxin-Induced PARP1/PARP2 Activation in Cells Using a Fluorescent Fusion Protein-Based Reporter
Published on: April 17, 2026
Asbestos exposure affects poly(ADP-ribose) polymerase-1 activity: role in asbestos-induced carcinogenesis
Marco Tomasetti1, Monica Amati, Linda Nocchi
1Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, viaTronto 10/A Torrette, 60020 Ancona, Italy. m.tomasetti@univpm.it
Abstract:
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.
Insights
Asbestos exposure may lead to malignant mesothelioma by impairing Poly(ADP-ribose) polymerase-1 (PARP1) activity. This dysfunction results in DNA instability and cell transformation, contributing to cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Environmental Health
Background:
- Asbestos exposure is a known cause of malignant mesothelioma (MM) and other asbestos-related diseases.
- Asbestos is genotoxic, inducing DNA strand breaks and apoptosis in lung cells.
- Poly(ADP-ribose) polymerase-1 (PARP1) functions as a DNA damage sensor.
Purpose of the Study:
- To investigate the role of PARP1 in asbestos-induced carcinogenesis.
- To evaluate PARP1 expression, activity, DNA damage, and repair in asbestos-exposed individuals and MM patients.
Main Methods:
- Assessed PARP1 expression and activity in circulating cells and pleural biopsies.
- Measured DNA damage (8-hydroxy-2'-deoxyguanosine) and DNA repair efficiency in lymphocytes.
- Induced cell transformation in immortalized mesothelial cells exposed to asbestos and a PARP1 inhibitor.
Main Results:
- Elevated PARP1 expression and 8-hydroxy-2'-deoxyguanosine accumulation were observed in asbestos-exposed subjects and MM patients.
- PARP1 expression was high, but its activity was low in both circulating cells and MM biopsies.
- Lymphocytes from MM patients showed low DNA repair efficiency.
- Asbestos exposure with PARP1 inhibition induced cell transformation in mesothelial cells.
Conclusions:
- Asbestos exposure may inhibit PARP1 activity, leading to increased DNA instability.
- This PARP1 dysfunction is proposed as a mechanism contributing to asbestos-induced malignant mesothelioma.
- Findings suggest a link between impaired DNA repair, PARP1 activity, and asbestos-related carcinogenesis.
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