Reactive oxygen species may participate in the mutagenicity and mutational spectrum of cadmium in Chinese hamster ovary-K1 cells

Chemical Research in Toxicology
J L YangJ G Lin

Abstract

The molecular nature of mutations induced by Cd was investigated in this study to elucidate the role of Cd in the initiation of carcinogenesis. Exposing Chinese hamster ovary (CHO)-K1 cells to cadmium acetate markedly decreased the colony-forming ability of cells and induced mutation frequency in the hypoxanthine (guanine) phosphoribosyltransferase (hprt) gene. The mutation frequency induced by Cd at LD30-LD20 doses was approximately 20 times that of untreated cells. D-Mannitol, a scavenger of reactive oxygen species (ROS), significantly protects cells against Cd cytotoxicity and mutagenicity. Furthermore, non-cytotoxic doses of 3-amino-1,2,4-triazole, a catalase inhibitor, potentiates Cd cytotoxicity and mutagenicity. The cellular Cd uptake ability was not altered by the combined treatment with either D-mannitol or 3-amino-1,2,4-triazole. The GSH level and the activities of GSH peroxidase, GSSG reductase, and catalase in cells treated with Cd (4 microM, 4 h) decreased to 78%, 47%, 40%, and 22% of the untreated cells, respectively. Those enzymatic activities recovered to normal levels 8 h after removing Cd. Polymerase chain reaction and DNA sequencing analysis of 54 independent Cd mutants revealed Cd-induced base substitutions,...Continue Reading

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Citations

Dec 4, 2003·Mutation Research·Michael P Waalkes
Feb 6, 2004·Mutation Research·Metka Filipic, Tom K Hei
Jun 1, 2000·Journal of Inorganic Biochemistry·K S Kasprzak, K Bialkowski
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Sep 29, 2011·Mutation Research·Metka Filipič
Mar 7, 2009·Biomedical and Environmental Sciences : BES·Jian-Lin LouShi-Jie Xu
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