Cadmium-induced Oxidative Cellular Damage in Human Fetal Lung Fibroblasts (MRC-5 Cells)
Cheng-Feng Yang,1 Han-Ming Shen,2 Yi Shen,2 Zhi-Xiong Zhuang,3 and Choon-Nam Ong2
1School of Public Health, Tongji Medical University, Wuhan, Peoples Republic of China; 2Department of Community, Occupational, and Family Medicine, National University of Singapore, Singapore; and 3School of Public Health, Sun Yet-Sen University of Medical Sciences, Guangzhou, Peoples Republic of China.
Abstract
Epidemiological evidence suggests that cadmium (Cd) exposure causes pulmonary damage such as emphysema and lung cancer. However, relatively little is known about the mechanisms involved in Cd pulmonary toxicity. In the present study, the effects of Cd exposure on human fetal lung fibroblasts (MRC-5 cells) were evaluated by determination of lipid peroxidation, intracellular production of reactive oxygen species (ROS), and changes of mitochondrial membrane potential. A time- and dose-dependent increase of both lactate dehydrogenase leakage and malondialdehyde formation was observed in Cd-treated cells. A close correlation between these two events suggests that lipid peroxidation may be one of the main pathways causing its cytotoxicity. It was also noted that Cd-induced cell injury and lipid peroxidation were inhibited by catalase and superoxide dismutase, two antioxidant enzymes. By using the fluorescent probe 2´,7´-dichlorofluorescin diacetate, a significant increase of ROS production in Cd-treated MRC-5 cells was detected. The inhibition of dichlorofluorescein fluorescence by catalase, not superoxide dismutase, suggests that hydrogen peroxide is the main ROS involved. Moreover, the significant dose-dependent changes of mitochondrial membrane potential in Cd-treated MRC-5 cells, demonstrated by increased fluorescence of rhodamine 123 examined using a laser-scanning confocal microscope, also indicate the involvement of mitochondrial damage in Cd cytotoxicity. These findings provide in vitro evidence that Cd causes oxidative cellular damage in human fetal lung fibroblasts, which may be closely associated with the pulmonary toxicity of Cd. Key words: cadmium, cytotoxicity, lipid peroxidation, mitochondrial membrane potential, MRC-5 cells, ROS. Environ Health Perspect 105:712-716 (1997)
Address correspondence to C.N. Ong, Department of Community, Occupational, and Family Medicine, National University of Singapore, Singapore 119074.
This research project was supported in part by the China Medical Board, New York, USA and the Program on Environmental and Occupational Health, Centre for Environmental and Occupational Health, National University of Singapore. The authors would like to thank H.Y. Ong, B.L. Lee, A.L. New, and M. Chan for their technical support.
Received 3 December 1996; accepted 1 April 1997.
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