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Lead and mercury mutagenesis: Role of H 2 O 2 , superoxide dismutase, and xanthine oxidase
Author(s) -
Ariza Maria E.,
Bijur Gautam N.,
Williams Marshall V.
Publication year - 1998
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/(sici)1098-2280(1998)31:4<352::aid-em8>3.0.co;2-k
Subject(s) - xanthine oxidase , superoxide dismutase , mutagenesis , mercury (programming language) , chemistry , biochemistry , enzyme , mutation , gene , computer science , programming language
It has been suggested that reactive oxygen intermediates (ROIs) may have a role in the genotoxic effects of lead (Pb 2+ ) and mercury (Hg 2+ ), but there have not been any definitive studies demonstrating a causal relationship between the induction of ROIs by these metals and mutagenesis. We previously demonstrated, using the transgenic Chinese hamster ovary cell line AS52, that low concentrations (0.1–1 μM) of Pb 2+ and Hg 2+ are mutagenic. In the present study, using a novel histochemical computer‐enhanced image analysis technique, we demonstrate that Pb 2+ and Hg 2+ induce the formation of H 2 O 2 in AS52 cells by at least two distinct mechanisms. One is characterized by the rapid induction of H 2 O 2 following treatment of cells with concentrations of Pb 2+ or Hg 2+ below 0.8 and 1 μM, respectively, while the second occurs in AS52 cells treated with concentrations of Pb 2+ or Hg 2+ greater than 0.8 and 1 μM, respectively. Pb 2+ and Hg 2+ (0.1–1 μM) had no effect on the activities of partially purified catalase, glutathione peroxidase, or glutathione reductase, important enzymes involved with antioxidant defense, but these metals stimulated the activities of copper‐zinc superoxide dismutase (CuZn‐SOD) and xanthine oxidase (XO). Allopurinol (50 μM), a specific inhibitor of xanthine oxidase, inhibited the induction of H 2 O 2 by Pb 2+ (0.8–1 μM) and Hg 2+ (1 μM) and also inhibited Pb 2+ ‐ and Hg 2+ ‐induced mutagenesis. These results demonstrate that Pb 2+ and Hg 2+ disrupt the redox status of AS52 cells by enhancing the activities of CuZn‐SOD and XO. Furthermore, the results of these studies also demonstrate that there is a causal relationship between the induction of H 2 O 2 by these metals and mutagenesis. Environ. Mol. Mutagen. 31:352–361, 1998. © 1998 Wiley‐Liss, Inc.