Short Communication
Increased cytotoxicity of cadmium in fibroblasts lacking c-fos

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Abstract

Cadmium has been known to induce the expression of the c-fos gene in various cell types including fibroblasts. To clarify the biological significance of c-fos induction by cadmium, mouse 3T3-like fibroblasts lacking c-fos were exposed to cadmium, and the resultant cellular damage was assayed by WST-8 (4-[3-(2-methoxy-4-nitrophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate sodium salt) conversion, trypan blue exclusion, or lactate dehydrogenase leakage. The c-fos-deficient cells (f1 and f10) were affected more severely than the wild-type cells (NIH 3T3 and f20) with respect to both cell growth and cellular damage following exposure to 10 or 20 μM cadmium chloride. These results suggest that c-fos may play a protective role against the cytotoxic effects of cadmium at least in these 3T3-like fibroblasts.

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Cell culture

The cell lines f20 (c-fos+/+), f1 (c-fos−/−), and f10 (c-fos−/−) (provided by Dr. E. F. Wagner, Research Institute of Molecular Pathology) are mouse 3T3-like fibroblasts immortalized from embryos obtained by mating c-fos+/− mice, and their characterizations have been described 8, 9. These 3T3-like and NIH 3T3 fibroblasts (Health Science Research Resources Bank) were grown in DMEM† supplemented with 10% heat-inactivated fetal bovine serum, 100 U/mL of penicillin and 100 μg/mL of streptomycin

Results

Cell growth was evaluated with the WST-8 assay (Fig. 1). In the absence of CdCl2, both c-fos+/+ (NIH 3T3 and f20) and c-fos−/− cells (f1 and f10) proliferated well, although some differences in the growth rate among the cell lines were seen. No cell line was affected by treatment with 1 μM CdCl2 for 2 days (data not shown). Incubation with 10 μM CdCl2 did not affect the growth of NIH 3T3 cells (Fig. 1A). However, incubation of NIH 3T3 cells with 20 μM CdCl2 for 2 or 3 days reduced the growth

Discussion

We found that c-fos−/− cells (f1 and f10) were affected more severely than c-fos+/+ cells (NIH 3T3 and f20) with respect to both cell growth and cellular damage following exposure to 10 or 20 μM CdCl2. These results indicated that the expression of the c-fos gene is not the major factor for the development of cellular damage caused by cadmium, but c-fos may play a protective role against the cytotoxic effects of cadmium at least in these 3T3-like fibroblasts. The difference in the sensitivity

Acknowledgements

We gratefully acknowledge receipt of the cell lines f20, f1, and f10 from Dr. K. Matsuo and Dr. E. F. Wagner (Research Institute of Molecular Pathology). This work was supported, in part, by a Grant-in-Aid for Science Research from the Ministry of Education, Science, Sports and Culture, Japan.

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