Altered expression of the DNA repair protein, N-methylpurine-DNA glycosylase (MPG), in breast cancer

AbstractWe examined expression of N-methylpurine-DNA glycosylase (MPG), a DNA repair enzyme that removes N-alkylpurine damage, in normal, malignant, and immortalized breast epithelial cells, and breast cancer cell lines (MDA-MB-231, MCF7, T47D). Northern analysis showed increased expression in cancer versus normal breast epithelial cells (2–24-fold). Southern blots revealed no gene amplification or polymorphisms. Immunofluorescence, immunohistochemistry, and Western blot analysis demonstrated increased MPG protein expression in the tumor cells that correlated with elevated glycosylase activity. Since MPG overexpression has been shown to be paradoxically associated with increased susceptibility to DNA damage, up-regulation of this gene may suggest a functional role in breast carcinogenesis

Viral hepatitis and agranulocytosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44381/1/10620_2005_Article_BF01071979.pd

Effects of Antioxidants on Oxidant-induced Sister Chromatid Exchange Formation

Abstract Introduction Stimulated human phagocytes produce sister chromatid exchanges in cultured mammalian cells by a mechanism involving oxygen metabolites. Experiments were designed to determine whether antioxidants inhibit this process. Superoxide dismutase, catalase, and hydroxyl radical scavengers (benzoate, mannitol) protected target Chinese hamster ovary cells from phagocyte-induced sister chromatid exchanges, implicating the involvement of hydroxyl radicals in this chromosomal damage. N-acetylcysteine and #l-carotene were also protective. a-Tocopherol (>5 gtM) protected target cells exposed to phagocytes but not to enzymatically generated oxidants when the vitamin was added just before the source of oxygen radicals, suggesting, as reported by others, that the principal action of tocopherol in this setting was to inhibit the release of oxidants from phagocytes. On the other hand, cultivation of target cells with supplemental tocopherol protected them from the toxic effects of the enzymatic oxidant-producing system, indicating a role for membrane-associated free radicals in the mechanism of sister chromatid exchange induction. Low concentrations of sodium selenite (0.1-1.0 ttM) protected the target cells. However, higher concentrations (10 igM) of selenite had no effect on oxidant-induced sister chromatid exchange formation, and 0.1 mM selenite increased the number of exchanges. Sodium selenite concentrations of 0.1 mM also decreased the intracellular glutathione concentration of target cells during an oxidant stress, and reducing target cell glutathione concentrations with buthionine sulfoximine increased their sensitivity to oxygen-related chromosomal damage. Therefore, the potentiation of oxygen radical-induced chromosomal damage observed with high concentrations of selenite may result from a decrease in the thiol antioxidant defense systems within the cell. The findings suggest that (a) the hydroxyl radical has an important role in the production of phagocyte-induced cytogenetic injury, (b