Cellular and molecular mechanism of arsenite toxicity

• Main Authors: Wang, Tsu Shing, 王祖興
• Other Authors: Huang Haimei
• Format: Others
• Language: en_US
• Published: 1996
• Online Access: http://ndltd.ncl.edu.tw/handle/32917417401016742613

博士 === 國立清華大學 === 輻射生物研究所 === 84 === Arsenic compounds are widely distributed natural toxicants.n vitro studies indicate that arsenic compounds can inducehromosome aberrations, sister-chromatid exchanges, and lung-pecific DNA strand break and DNA-protein crosslinking. Chronicxposures to arsenic increase the incidence of skin, lung, bladdernd possibly liver cancer in human beings. The molecularechanism of arsenic induced cancer is largely unknown, althoughnvolvement of free radicals has been suggested. Since the X-rayensitive Chinese hamster ovary cells, xrs-5 are also o several free-radicals generating agents, including H2 O2, we sed this cell line to test whether the genotoxic effect of ediated via the generation of reactive oxygen species (ROS).he results indicate that the xrs-5 cells were also more sensitive rsenite in terms of cell-killing and micronuclei (MN) induction omparison to the parental CHO-K1 cells. The level of arsenicptake and release, the levels of elementary components forrsenic detoxification, such as glutathione, glutathione S-ransferase (GST), glutathione reductase (GSHR), superoxideismutase (SOD) were similar in these two cell lines. Thectivities of catalase and glutathione peroxidase (GPx), however,ere 6- and 7-fold lower, respectively in the xrs-5 cells inomparison to the CHO-K1 cells. Moreover, extra-cellular additionf Cat or GPx, could effectively reduce the frequency of arsenite-nduced MN. Pretreating CHO-K1 cells with mercaptosuccinate,n inhibitor of GPx, enhanced the MN induction by arsenite and2O2. Simultaneous treatment with mercaptosuccinate and 3-minotriazole, an inhibitor of Cat, synergistically increased nduced MN. Furthermore, sodium selenium, a stimulator of Gpxctivity, significantly reduced arsenite- and H2 O2-induced MN.