title: Effects of cadmium on cell proliferation, apoptosis, and proto-oncogene expression in zebrafish liver cells.
abstract: Cadmium (Cd) is one of the major transitional metal that has toxic effects in aquatic organisms and their associated ecosystem; however, its hepatic toxicity and carcinogenicity are not very well characterized. We used a zebrafish liver (ZFL) cell line as a model to investigate the mechanism of Cd-induced toxicity on hepatocytes. Our results showed that Cd can be effectively accumulated in ZFL cells in our exposure experiments. Cell cytotoxicity assays and flow cytometer measurements revealed that Cd(2+) stimulated ZFL cell proliferation with decreasing apoptotic cell numbers indicating potentially tumorigenic effects of Cd in ZFL cells. Gene expression profiles also indicated that Cd downregulated oncogenes p53 and rad51 and upregulated immediate response oncogenes, growth arrest and DNA damage-inducible (gadd45) genes, and growth factors. We also found dramatic changes in the gene expression of c-jun and igf1rb at different exposure time points, supporting the notion that potentially tumorigenic of Cd-is involved in the activation of immediate early genes or genes related to apoptosis in cancer promotion.
authors.affiliation: School of Life Sciences, Chinese University, Sha Tin, N.T., Hong Kong SAR, China.
authors.forename: Ying Ying
authors.initials: YY
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Chinese University, Sha Tin, N.T., Hong Kong SAR, China.
authors.forename: Jin Yong
authors.initials: JY
authors.lastname: Zhu
authors.affiliation: School of Life Sciences, Chinese University, Sha Tin, N.T., Hong Kong SAR, China. Electronic address: kingchan@cuhk.edu.hk.
authors.forename: King Ming
authors.initials: KM
authors.lastname: Chan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D011519:Proto-Oncogenes / Q000235:genetics*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000502:physiology*
chemical_list: D014874:Water Pollutants, Chemical; D002104:Cadmium
keywords: Apoptosis; Carcinogenesis; Cell proliferation; Oncogene