Analysis of cadmium mutageness in Chinese hamster ovary cells
- Univ. of Texas Medical Branch, Galveston, TX (United States)
We have shown earlier that physical and chemical agents which are known to generate reactive oxygen species (ROS) are more mutagenic to the autosomal heterozygous gpt gene in CHO cell derivative, AS52 than to the X-linked hemizygous hprt locus in CHO cell clone K1-BH4. These ROS generating agents primarily induced deletions in both assays as analyzed at the cellular level. We have reported previously that cadmium (Cd) is mutagenic at both the gpt gene in AS52 cells and the hprt locus in K1-BH4 cells but more mutagenic to the gpt gene in AS52 cells. The molecular nature of Cd-induced mutants is being studied using polymerase chain reaction (PCR)-directed deletion screening and DNA sequencing method. 75 independent Cd-induced mutants is being studied using polymerase chain reaction (PRC)-directed deletion screening and DNA sequencing method. 75 independent Cd-induced HPRT{sup -} mutants were analyzed by the multiplex in vitro DNA amplification. Of these mutants 30 (40%) were found to have large deletions. The deletions included single and multiple exons. Total hprt gene deletions were found in 13 mutants. We have also been investigating the modulative role of glutathione by L-buthionein-SR-sulfoximine(BSO) and metallionein by zinc on Cd mutagenesis. The effect of zinc pretreatment on the cytotoxicity of Cd showed that treatment of AS52 cells with 0.5x10{sup -4} M zinc acetate for 7 h prior to Cd exposure produced lower toxicity. The effect of zinc-pretreatment on the mutagenicity of Cd showed that there were lower mutagenic responses in AS52 cells pretreated with 0.5x10{sup -4} M zinc. Experiments with pretreatment of BSO are in progress.
- OSTI ID:
- 88882
- Report Number(s):
- CONF-9405324-; ISSN 0893-6692; CNN: Grant R819387; TRN: 95:004220-0022
- Journal Information:
- Environmental and Molecular Mutagenesis, Vol. 23, Issue Suppl.23; Conference: 25. annual meeting of the Environmental Mutagen Society, Portland, OR (United States), 7-12 May 1994; Other Information: PBD: 1994
- Country of Publication:
- United States
- Language:
- English
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