Alteration of cadmium-induced mutational spectrum by catalase depletion in Chinese hamster ovary-K1 cells

Jui-I Chao, Jia Ling Yang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Previously, we have demonstrated that cadmium acetate significantly induces hprt mutation frequency in Chinese hamster ovary (CHO)-K1 and that 3-amino-1,2,4-triazole (3AT), a catalase inhibitor, potentiates the mutagenicity of cadmium [Chem. Res. Toxicol. 9 (1996) 1360-1367]. In this study, we investigate the role of intracellular peroxide in the molecular nature of mutations induced by cadmium. Using 2′,7′-dichlorofluorescin diacetate and fluorescence spectrophotometry, we have shown that cadmium dose-dependently increased the amounts of intracellular peroxide and the levels were significantly enhanced by 3AT. Furthermore, we have characterized and compared the hprt mutation spectra in 6-thioguanine-resistant mutants derived from CHO-K1 cells exposed to 4μM of cadmium acetate for 4h in the absence and presence of 3AT. The mutation frequency induced by cadmium and cadmium plus 3AT was 11- and 16-fold higher than that observed in untreated populations (2.2 × 10-6), respectively. A total of 40 and 51 independent hprt mutants were isolated from cadmium and cadmium plus 3AT treatments for mRNA-polymerase chain reaction (PCR), genomic DNA-PCR and DNA sequencing analyses. 3AT co-administration significantly enhanced the frequency of deletions induced by cadmium. Cadmium induced more transversions than transitions. In contrast, 3AT co-administration increased the frequency of GC → AT transitions and decreased the frequencies of TA → AT and TA → GC transversions. Together, the results suggest that intracellular catalase is important to prevent the formation of oxidative DNA damage as well as deletions and GC → AT transitions upon cadmium exposure.

Original languageEnglish
Pages (from-to)7-18
Number of pages12
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume498
Issue number1-2
DOIs
StatePublished - 15 Nov 2001

Keywords

  • Base substitution
  • Cadmium
  • Deletion
  • Intracellular peroxide
  • hprt

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