Elevated 8-oxo-7,8-dihydro-2'-deoxyguanosine in genome of T24 bladder cancer cells induced by halobenzoquinones

Halobenzoquinones（HBQs） are an emerging class of halogenated disinfection byproducts（DBPs） in drinking water, which raised public concerns due to potential carcinogenic effects to human bladder. Our previous work demonstrated that HBQs and hydrogen peroxide（H_2O_2）together generated oxidative DNA damage via a metal-independent and intercalationenhanced oxidation mechanism in vitro. This study further investigated the efficiency of various HBQs to induce oxidative DNA damage in T24 bladder cancer cells. Compared with T24 cells without treatment（3.1 lesions per 10~6 d G）, the level of 8-oxo-7,8-dihydro-2′-deoxyguanosine（8-oxod G） significantly increased by 1.4, 3.2, 8.8, and 9.2 times after treatment with tetrabromo-1,4-benzoquinone（TBBQ）, terachloro-1,4-benzoquinone（TCBQ）,2,6-dichloro-1,4-benzoquinone（2,6-DCBQ） and 2,5-dichloro-1,4-benzoquinone（2,5-DCBQ） for24 hr, respectively. Interestingly, we found that the oxidative potency of HBQs in T24 cells（2,5-DCBQ ≈ 2,6-DCBQ 〉 TCBQ 〉 TBBQ） is inconsistent with that of in vitro ds DNA oxidation（TCBQ 〉 TBBQ 〉 2,5-DCBQ 〉 2,6-DCBQ）, suggesting HBQs induce oxidative lesions in cellular genomic DNA probably involved with a complex mechanism.

Neuroprotective Effects of Electroacupuncture Preventive Treatment in Senescence-Accelerated Mouse Prone 8 Mice

Objective： To investigate the preventive treatment effects of electroacupuncture（EA） on cognitive changes and brain damage in senescence-accelerated mouse prone 8（SAMP8） mice. Methods： The 5-month-old male SAMP8 and age-matched homologous normal aging mice（SAMR1） were adopted in this study. EA stimulation at Baihui（GV 20） and Yintang（EX-HN 3） was performed every other day for 12 weeks, 4 weeks as a course. Morris water maze test and Nissl-stained with cresyl violet were used for cognitive impairments evaluation and brain morphometric analysis. Amyloid-β（Aβ） expression in hippocampus and parietal cortex was detected by immunohistochemistry, and apoptosis was observed by TUNEL staining. Results： After 3 courses of EA preventive treatment, the escape latencies of 8-month-old SAMP8 mice in EA group were significantly shortened than those of un-pretreated SAMP8 mice. Compared with SAMR1 mice, extensive neuronal changes were visualized in the CA1 area of hippocampus in SAMP8 mice, while these pathological changes and attenuate cell loss in hippocampal CA1 area of SAMP8 mice markedly reduced after EA preventive treatment. Furthermore, Aβ expression in hippocampus and parietal cortex of SAMP8 mice decreased significantly after EA treatment, and neuronal apoptosis decreased as well. Conclusion： EA preventive treatment at GV 20 and EX-HN 3 might improve cognitive deficits and neuropathological changes in SAMP8 mice, which might be, at least in part, due to the effects of reducing brain neuronal damage, decreasing neuronal apoptosis and inhibiting Aβ-containing aggregates.