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Arsenic trioxide (As2 O3 ) is commonly used to treat acute promyelocytic leukemia and solid tumors. However, the clinical application of the agent is limited by its cyto- and genotoxic effects on normal cells. Thus, relief of As2 O3 toxicity in normal cells is essentially necessary for improvement of As2 O3 -mediated chemotherapy. In this study, we have identified a series of protective effects of resveratrol against As2 O3 -induced oxidative damage in normal human bronchial epithelial (HBE) cells. We showed that treatment of HBE cells with resveratrol significantly reduced cellular levels of DNA damage, chromosomal breakage, and apoptosis induced by As2 O3 . The effect of resveratrol against DNA damage was associated with a decreased level of reactive oxygen species and lipid peroxidation in cells treated by As2 O3 , suggesting that resveratrol protects against As2 O3 toxicity via a cellular anti-oxidative stress pathway. Further analysis of the roles of resveratrol demonstrated that it modulated biosynthesis, recycling, and consumption of glutathione (GSH), thereby promoting GSH homeostasis in HBE cells treated by As2 O3 . This was further supported by results showing that resveratrol prevented an increase in the activities and levels of caspases, Fas, Fas-L, and cytochrome c proteins induced by As2 O3 . Our study indicates that resveratrol relieves As2 O3 -induced oxidative damage in normal human lung cells via maintenance of GSH homeostasis and suppression of apoptosis.

5&rsquo, 8-Cyclo-2&rsquo, deoxyadenosine (cdA), in the 5&rsquo, R and 5&rsquo, Sdiastereomeric forms, are typical non strand-break oxidative DNA lesions, induced by hydroxyl radicals, with emerging importance as a molecular marker. These lesions are exclusively repaired by the nucleotide excision repair (NER) mechanism with a low efficiency, thus readily accumulating in the genome. Poly(ADP-ribose) polymerase1 (PARP1) acts as an early responder to DNA damage and plays a key role as a nick sensor in the maintenance of the integrity of the genome by recognizing nicked DNA. So far, it was unknown whether the two diastereomeric cdA lesions could induce specific PARP1 binding. Here, we provide the first evidence of PARP1 to selectively recognize the diastereomeric lesions of 5&rsquo, S-cdA and 5&rsquo, R-cdA in vitro as compared to deoxyadenosine in model DNA substrates (23-mers) by using circular dichroism, fluorescence spectroscopy, immunoblotting analysis, and gel mobility shift assay. Several features of the recognition of the damaged and undamaged oligonucleotides by PARP1 were characterized. Remarkably, PARP1 exhibits different affinities in binding to a double strand (ds) oligonucleotide, which incorporates cdA lesions in R and S diastereomeric form. In particular, PARP1 proved to bind oligonucleotides, including a 5&rsquo, S-cdA, with a higher affinity constant for the 5&rsquo, S lesion in a model of ds DNA than 5&rsquo, R-cdA, showing different recognition patterns, also compared with undamaged dA. This new finding highlights the ability of PARP1 to recognize and differentiate the distorted DNA backbone in a biomimetic system caused by different diastereomeric forms of a cdA lesion.