Evidence for induction of oxidative stress caused by chronic exposure of Chinese residents to arsenic contained in drinking water.

Exposure of experimental animals or cultured cells to arsenic induces oxidative stress, but, to date, no examination of this phenomenon in humans has been reported. In this study we conducted a cross-sectional study in Wuyuan, Inner Mongolia, China, to explore the relationship between chronic arsenic exposure from drinking water and oxidative stress in humans. Thirty-three inhabitants who had been drinking tube-well water with high concentrations of inorganic arsenic (mean value = 0.41 mg/L) for about 18 years constituted the high-exposure group, and 10 residents who lived nearby but were exposed to much lower concentrations of arsenic in their drinking water (mean value = 0.02 mg/L) were selected as the low-exposure comparison group. Results of the present study indicated that although the activity for superoxide dismutase (SOD) in blood did not differ significantly between the two groups, the mean serum level of lipid peroxides (LPO) was significantly higher among the high-exposed compared with the low-exposed group. Elevated serum LPO concentrations were correlated with blood levels of inorganic arsenic and its methylated metabolites. In addition, they showed an inverse correlation with nonprotein sulfhydryl (NPSH) levels in whole blood. The subjects in the high-arsenic-exposure group had mean blood NPSH levels 57.6% lower than those in the low-exposure group. Blood NPSH levels were inversely correlated with the concentrations of inorganic arsenic and its methylated metabolites in blood and with the ratio of monomethylarsenic to inorganic arsenic. These results provide evidence that chronic exposure to arsenic from drinking water in humans results in induction of oxidative stress, as indicated by the reduction in NPSH and the increase in LPO. Some possible mechanisms for the arsenic-induced oxidative stress are discussed.

Heterogeneity of ovarian cancer: relationships among histological group, stage of disease, tumor markers, patient characteristics, and survival.

Epidemiological studies have established associations between various reproductive factors and risk of ovarian cancer; it has also been observed that some of these risk factors are only associated with specific histological subgroups. To investigate the correlation of genetic alterations with these risk factors, we examined a consecutive series of 158 ovarian cancer cases treated at the University of Kentucky (1990-96). Common molecular genetic alterations (LOH on chromosome 17, P53 alterations, K-RAS mutations), histological and clinical characteristics of the disease, demographic patient information and survival were evaluated. These latter data were from the Kentucky Cancer Registry. Univariate analysis showed higher frequencies of chromosome 17 loss and P53 mutations in tumors of advanced stage and grade, and in older and post-menopausal women. Non-mucinous tumors were more likely to be classified as late stage, high-grade cancers, and to have chromosome 17 loss and P53 mutations. Survival analysis indicated that stage was the only independent significant variable. When stage was the outcome variable in multiple logistic regression analysis, histology and chromosome 17 loss were significantly associated with poor survival. This case-case study provides evidence that ovarian cancers of mucinous and non-mucinous histology are significantly different with respect to clinical characteristics, survival and molecular alterations. It also lends support to the hypothesis that ovarian cancer is a heterogeneous disease with distinct etiological factors and clinical outcomes, which may require different approaches to treatment.