Role of DNA polymerase beta in the genotoxicity of arsenic

• DOI: 10.1002/em.20643
• Publication Date: 2011-03-04T10:25:23Z
• Authors: Yanhao Lai; Wei Zhao; Chen Chen; Mei Wu; Zunzhen Zhang
• Keywords: DNA polymerase beta

Arsenic, an important hazard in the environment, is associated with human cancer and other degenerative diseases. However, mechanisms underlying arsenic hazardous effects remain unclear. It has been reported exposure can result increased cellular reactive oxygen species oxidative DNA damage. This suggests base excision repair (BER), major pathway for repairing damage, may be involved combating effects. As a critical enzyme BER, polymerase beta (Pol β) might play essential role reducing toxicity. To test this hypothesis, we evaluated arsenic-induced cytotoxic genotoxic under Pol β deficiency. Our results demonstrated that viability of β-deficient mouse embryonic fibroblasts was much lower than wild-type cells after treatment arsenite (As(3+) ). An level damage significantly delayed arsenite-induced indicated reduced lesions consistent increase frequency micronuclei (MN), indicator chromosomal breakage, which also observed treated arsenite. In contrast, harboring overexpressed resulted MN cells, indicating overexpression combat conclusion, our indicate maintaining integrity further suggest deficiency BER genotoxicity carcinogenicity.