Induction of superoxide dismutase, chromosomal aberrations and sister-chromatid exchanges by paraquat in Chinese hamster fibroblasts

Abstract

We have recently shown that Bloom syndrome fibroblasts have elevated levels of superoxide dismutase activity compared to those of normal fibroblasts. Based on this observation we decided to test whether an increased rate of superoxide radical production could be responsible for the induction of superoxide dismutase and of chromosomal aberrations and sister-chromatid exchanges characteristic of Bloom syndrome. Utilizing the superoxide-generating herbicide paraquat in Chinese hamster fibroblasts, we assayed the cells for dismutase activity, chromosomal aberrations and sister-chromatid exchanges. All 3 parameters investigated demonstrated a dose-dependent increase with paraquat and, consequently, with the superoxide produced. Since the induction of the enzyme is mediated by its substrate, the superoxide anion radical, we concluded that the increased dismutase activity (in Bloom syndrome and paraquat-treated cells) may be a secondary manifestation of an overall imbalance in oxygen metabolism and that this elevated enzymatic activity is insufficient to detoxify the high superoxide levels, which results in elevated levels of chromosomal damage.