Anti-XPA polyclonal antibody

XPA, a zinc-finger DNA-binding protein, play an important role in both global genome and transcription-coupled repair pathways. XPA -4G>A polymorphism was identified in the 5' noncoding region, located four nucleotides upstream of the ATG start codon. Previous studies have shown that this polymorphism may affect mRNA tertiary structure and stability and play a role in susceptibility to cancer. However, the results remained controversial. To derive a more precise estimation of association between this polymorphism and risk of different types of cancer, we performed a meta-analysis based on 36 casecontrol or casecohort studies, including a total of 11,700 cases and 15,033 controls. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, no significantly elevated cancer risk was found in all genetic models when eligible studies were pooled into the meta-analysis. In the stratified analyses, we found that individuals with A-allele had a higher risk of lung cancer (AA versus GG: OR = 1.25, 95% CI = 1.091.43; recessive model: OR = 1.31, 95% CI = 1.161.48). When stratified by ethnicity, significantly elevated risks were observed among Asian populations (AA versus GG: OR = 1.31, 95% CI = 1.011.70; dominant model: OR = 1.14, 95% CI = 1.001.30). This meta-analysis suggests that XPA -4G>A polymorphism is associated with increased lung cancer risk and may be a low-penetrant risk factor in Asian ethnicity for cancer development.

Genotoxic potentials and the mechanisms of six pharmaceuticals, which are frequently detected in surface water worldwide, were investigated using isogenic chicken DT40 mutant cell lines. These pharmaceuticals include erythromycin, sulfamethazine, sulfathiazole, chlortetracycline, oxytetracycline, and diclofenac. The genotoxic effects of these pharmaceuticals were determined based on growth kinetics of several mutant cell lines. Genotoxic chemicals were expected to decrease the growth kinetics in at least one of the mutants more significantly than DNA-repair-proficient wild-type cells. The test pharmaceuticals sensitized the cells deficient in homologous recombination (HR) repair (RAD54(-/-)), nucleotide excision repair (XPA(-/)), or translesion DNA synthesis (REV3(-/-)), suggesting that these pharmaceuticals may induce bulky adducts covalently bound to duplex DNA, like ultraviolet (UV) light. Genotoxicity was confirmed again by analyzing chromosome aberrations (CAs) and gamma-H2AX foci in both wild-type and the susceptible mutants (i.e., RAD54(-/-) and XPA(-/)) following the exposure to all the test pharmaceuticals except for erythromycin. The data indicate that these pharmaceuticals induce the DNA damages that stall DNA replication, leading to chromosomal breaks as well as translesion DNA synthesis mediated mutagenesis in DT40 cells. (C) 2012 Elsevier Ireland Ltd. All rights reserved.