Modulation of hypersensitivity to oxidative DNA damage in ATM defective cells induced by potassium bromate by inhibition of the Poly (ADP-ribose) polymerase (PARP).

Author(s) Mosesso, P.; Piane, M.; Pepe, G.; Cinelli, S.; Chessa, L.
Journal Mutat Res
Date Published 2018 Dec
Abstract

The ataxia telangiectasia mutated (ATM) protein is a pivotal multifunctional protein kinase predominantly involved in DNA damage response, as well as in maintaining overall functional integrity of the cells. Apart from playing its major role in regulating the cellular response to DNA damage, ATM, when mutated, can additionally determine oxidative stress, metabolic syndrome, mitochondrial dysfunction and neurodegeneration. In the present paper we aim to investigate the levels of oxidative stress potentially induced by the oxidizing rodent renal carcinogen KBrO in ATM-defective lymphoblastoid cell lines (LCLs) established from four classical AT patients (with different ATM mutations), one AT variant with reduced hypersensitivity to X rays, obligate AT heterozygotes and wild type intrafamilial control. A possible modulatory involvement of PARP in potentially induced oxidative stress is also evaluated following its inhibition with 3-aminobenzamide (3-AB). Treatments with KBrO clearly showed a marked hypersensitivity of the ATM-defective LCLs, including the AT variant. A marked and statistically significant reduction of KBrO-induced chromosomal damage following inhibition of PARP by 3-AB, was observed in all AT LCLs, but not in those from the AT variant, AT heterozygotes and wild type intrafamilial control. This result is suggestive of a modulatory involvement of PARP in the hypersensitivity of ATM-defective cells to DNA oxidative damage.

DOI 10.1016/j.mrgentox.2018.05.009
ISSN 1873-135X
Citation Mosesso P, Piane M, Pepe G, Cinelli S, Chessa L. Modulation of hypersensitivity to oxidative DNA damage in ATM defective cells induced by potassium bromate by inhibition of the Poly (ADP-ribose) polymerase (PARP). Mutat Res. 2018;836(Pt A):117-123.

Related Applications, Forms & Industries