Genotoxicity of lead, cadmium and arsenic in cultured mammalian cells (A{sub L})
- Colorado State Univ., Ft. Collins, CO (United States); and others
Heavy metal(s) cause tympanic and neurologic damage in humans. Although implicated in cancer and birth defects, metals have been weakly mutagenic in bacterial and mammalian cell assays. We have, therefore, studied genotoxic effects of arsenic [NaASO{sub 2}], cadmium [CdCl{sub 2}], and lead [Pb(C{sub 2}H{sub 3}O{sub 2})] in the human X hamster hybrid A{sub L} cells which were constructed so as to detect low level mutagenicity. A{sub L} cells contain one human chromosome, no. 11, in a Chinese hamster ovary (CHO) background. Mutations affecting MIC1 gene are detected via a complement-mediated toxicity assay in which cells expressing the S1 antigen encoded by MIC1 are killed: S1{sup -} mutants survive. The MIC1 gene is not hostage to neighbor genes so that mutations of any size in chromosome 11 are detectable. We found that suppression of glutathione (GSH) by BSO (buthione-S,R-sulfoximine) made Pb and Cd more lethal to A{sub L} cells. The LD{sub 50}s for Pb were 25 and 4 {mu}g/ml without and with BSO, respectively. For Cd these values were 0.3 and 0.08 {mu}g/ml respectively. The LD{sub 50} of As was 0.8 {mu}g/ml; BSO`s effect was not determined. In mutation studies at the S1{sup -} locus, lead`s slight activity was increased 10 fold by BSO (from 4 to 40 mutants/10{sup 6} clonable cells/{mu}g). Arsenic without BSO was mutagenic (140 mutants/LD{sub 50}); Cd was not. These mutagenic activities are 1/10 to 1/100 less than {sup 137}Cs-{gamma} rays. These results further demonstrate the value of the A{sub L} assay in evaluating weak mutagens.
- OSTI ID:
- 530849
- Report Number(s):
- CONF-9704100-; ISSN 0893-6692; TRN: 97:003016-0022
- Journal Information:
- Environmental and Molecular Mutagenesis, Vol. 29, Issue Suppl.28; Conference: 28. annual meeting of the Environmental Mutagen Society, Minneapolis, MN (United States), 19-23 Apr 1997; Other Information: PBD: 1997
- Country of Publication:
- United States
- Language:
- English
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