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Purpose Pterygium is an invasive and highly vascularized growth, thought to arise from activated and proliferating limbal epithelial stem cells. Epidemiologic studies have found the increase of active angiogenic and epithelial growth factors in pterygia, and implicated that these molecules could be involved directly or indirectly in the pathogenesis of pterygia as causative factors. The aim of this study was to investigate the association of polymorphisms of transforming growth factor (TGF) and vascular endothelial growth factor (VEGF) with pterygium.Methods A total of 133 pterygium patients and 105 volunteers without pterygium were enrolled in this study. Polymerase chain reaction based restriction fragment length polymorphism analysis was used to resolve the TGF-β1–509 and VEGF-460 genotypes.Results There was no significant difference in the allele frequency or genotype of TGF-β1–509 or VEGF-460 between total pterygium and the control group. No interaction between TGF-β1–509 and VEGF-460 was found either.Conclusions These results indicate that TGF-β1–509 and VEGF-460 polymorphisms were not highly associated with the pathology of pterygium. However, it may still be worthwhile to continue to search for angiogenic gene polymorphisms in order to predict the development of pterygium.

We report here that sequential digestion with endonuclease III, formamidopyrimidine-DNA glycosylase, and proteinase K in Tris buffer markedly increased the sensitivity for detecting DNA damage in arsenic-treated cells. These three enzymes increased DNA strand breaks in an additive manner. By using this sequential-enzyme-digestion comet assay, we demonstrated that trivalent inorganic arsenic induced more DNA damage than monomethylarsonous acid, monomethylarsonic acid, and dimethylarsinic acid in human blood cell lines. However, trivalent inorganic arsenic was far less potent than monomethylarsonous acid in inhibiting pyruvate dehydrogenase activity. Therefore, different mechanisms are involved in inhibiting pyruvate dehydrogenase activity and inducing DNA damage. Our results also indicate while trivalent inorganic arsenic induced more endonuclease III-digestible adducts, monomethylarsonous acid and monomethylarsonic acid induced more proteinase K-digestible adducts. These results suggest there is a difference in the mechanism for inducing DNA damage between inorganic and organic methylated arsenic compounds.

Arsenite is a human carcinogen reported to inhibit DNA repair. The binding of arsenite to functional thiol groups of DNA repair enzymes has in the past been suggested as a possible mechanism for the effect of arsenite on DNA repair. However, recent studies indicate that reactive oxygen species and nitric oxide are involved in arsenite toxicity. This research aims to elucidate the role of these possible mechanisms in the inhibition of UV-induced DNA repair by arsenite. As arsenite inhibits UV-DNA repair in Chinese hamster ovary cells, and this is a commonly used cell line for UV repair experiments, we used these cells to examine the effect of arsenite on the expression of UV-irradiated reporter genes. The T4 UV endonuclease V-incorporated comet assay was used to examine specifically the effect of arsenite on pyrimidine dimer excision. We showed that inhibition of UV-DNA repair by arsenite was suppressed by nitric oxide synthase inhibitors. Arsenite increased nitric oxide production and nitric oxide generators inhibited UV-DNA repair. The involvement of nitric oxide in the inhibition of pyrimidine dimer excision by arsenite was also confirmed in human fibroblasts. Investigation into the effect of oxidant modulators did not give a clear indication that reactive oxygen species are involved in arsenite inhibition of UV-DNA repair. Phenylarsine oxide, a strong thiol-reacting agent, did not inhibit pyrimidine dimer excision and also did not increase nitric oxide production. Our results show conclusively that nitric oxide is involved in the inhibition of pyrimidine dimer excision by arsenite. Reactive oxygen species and the binding of arsenite to functional thiol groups of DNA repair enzymes do not appear to be involved.

Recently, arsenic trioxide (As2O3) was reported to induce clinical remission in patients with acute promyelocytic leukemia. Modulation of protein phosphorylation by binding to the vicinal thiols has been suggested as a possible mechanism. We found that phenylarsine oxide, a strong vicinal thiol-binding agent, neither induced nuclear fragmentation or DNA laddering nor increased caspase activity in NB4 cells; however, As2O3 and a weak thiol-binding agent, dimethylarsinic acid, did increase activity. Dithiothreitol (DTT) effectively suppressed the phenylarsine oxide-inhibited cellular reductive capacity, but unexpectedly, enhanced As2O3-induced apoptosis in NB4 cells. As2O3-induced and As2O3-plus-DTT-induced apoptosis in NB4 cells was modulated by oxidant modifiers, but not by nitric oxide synthase inhibitors. These results demonstrate that DTT, a dithiol agent and known antidote for trivalent inorganic arsenic, enhances the toxicity of As2O3, thereby opening a new research direction for the mechanisms of arsenic toxicity and perhaps also helping in the development of new therapeutic strategies for treating leukemias.

Exposure to x-irradiation in uteroor during the early postnatal life (total body or head alone) produced a suppression of the development of hexobarbital metabolising enzyme system in liver. Abscopal inhibition of the hepatic enzyme system after x-irradiation was also noted in adult male rats, but with higher radiation doses, suggesting that the central nervous system plays a regulatory role not only in the development but also in the maintenance of optimal level of enzyme activity in liver.