Carcinogenesis, Vol 19, 881-888, Copyright © 1998 by Oxford University Press
YS Hwua and JL Yang
Cadmium and lead have been shown to induce cellular transformations and
gene mutations in cultured rodent cells, as well as tumours in live
animals. However, the mechanisms by which these metals cause cellular
transformations and mutations in human cells have not been explored. In
this study, we investigated the abilities of cadmium and lead to induce
anchorage-independent transformations and hprt gene mutations in diploid
human fibroblasts. Human fibroblasts were exposed to either cadmium acetate
(0-60 microM) or lead acetate (0-2 mM) for 24 h. After removal of the
metals, the cells were kept in exponential growth for 7 and 9 days before
mutation and anchorage-independence assays were taken, respectively. Both
cadmium and lead significantly induced anchorage-independent colonies in
dose-dependent manners; the frequencies of anchorage-independent colonies
induced by these metals were similar to those induced by
N-methyl-N'-nitro-N-nitrosoguanidine at approximately equal cytotoxic dose
ranges (30-10% survival). 3- Aminotriazole at non-cytotoxic dosages
decreased catalase activity by >80%, and markedly enhanced
cadmium-induced cytotoxicity and anchorage- independent colonies. Cadmium
uptake by human fibroblasts was not affected by 3-aminotriazole
co-administered with 10 microM of cadmium; whereas cadmium uptake and
accumulation were enhanced 1.5-fold by 3- aminotriazole co-administered
with 1-2.5 microM of cadmium. Lead- induced anchorage-independence or
cytotoxicity was not affected by 3- aminotriazole co-treatment; however,
3-aminotriazole did significantly enhance lead uptake and accumulation in
human fibroblasts. Neither cadmium- nor lead-induced
6-thioguanine-resistant mutation frequency in human fibroblasts.
Co-administering these metals with 3-aminotriazole did not enhance
mutations in human fibroblasts. These results suggest that cadmium and lead
may both act as tumour promoters in diploid human fibroblasts, and that
reactive oxygen species is more important in cadmium- than lead-induced
cytotoxicity and anchorage-independence.
ARTICLES
Effect of 3-aminotriazole on anchorage independence and mutagenicity in cadmium- and lead-treated diploid human fibroblasts
Department of Life Sciences, National Tsing Hua University, Taiwan, Republic of China.
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