| Cadmium, a heavy metal, is a member of group IIb in the periodic table of elements which is present in soils, sediments, air and water. Major occupational exposure occurs in non-ferrous metal smelters, in the production and processing of cadmium, its alloys and compounds and, increasingly, in the recycling of electronic waste. Non-occupational exposure is mainly from diet and smoking which contains relatively high concentrations of this element.Cadmium is listed by the US Environmental Protection Agency as one of 126 priority pollutants. In most studies, the half-life of cadmium in humans is estimated to be between 15 and 20 years. It can cause osteoporosis, irreversible renal tubular injury, anemia, eosinophilia, anosmia and chronic rhinitis.Cadmium is a potent human carcinogen and occupational exposure to it has been associated with cancers of the lung, the prostate, the pancreas, and the kidney. Because of its characteristics as a lung carcinogen, cadmium has been classified as a category 1 carcinogen (human carcinogen) by the International Agency for Research on Cancer and the National Toxicology Program of the USA. Furthermore, an association between human prostate cancer and cadmium was found, but has been considered controversial.A lot of investigations about the cytotoxicity and carcinogenicity of cadmium were done over the world and those studies for molecular mechanism of cadmium carcinogenicity were paid more attention to, however, the concrete mechanism is still unclear. It has been found that cadmium could cause genetic toxicity directly and indirectly, such as cause DNA strand break, DNA and protein cross-link, oxidative DNA damage and chromatosome anisotrophy, and those genetic toxicities may contribute to carcinogenesis. Cadmium could activate and inactivate many cellular genes and proteins. It was reported that tumor repression gene p53 and proto-oncogenes (c-jun, c-fos and c-myc) could be activated by cadmium. As an important tumor repression gene, p53 could induce apoptosis after DNA damage in mammal cells and involve in DNA repair and cell cycle checkpoint. We employed two methods toinactivate p53 in order to study what the role p53 play in DNA damage, cell cycle checkpoint, DNA synthesis process.In comet assay, it has been found that cadmium could induce DNA damage in both p53-efficient and p53-deficient fibroblast cells, and further induce p53-independent rapid G2 checkpoint and p53-dependent delay G2 checkpoint. It also has been demonstrated that cadmium could inhibit DNA synthesis. In different cell stages treated with cadmium, cells in G2/M stages were more sensitive than the cells in G1. It may be suggested that G2/M stage was the target stage of cadmium. Gadd45, as an important protein in G2/M cells transition, may play a key role in the induction of p53- and ATM-independent rapid G2 checkpoint.Isoflavones, a kind of phytoestrogen, is similar with 17-β estrogen in structure but the estrogen activity is very low. Epidemiological studies, animal experiments and cell culture found that isoflavones could prevent cancer and inhibit the reproduction of cancer cells. The present results showed that isoflavones could inhibit the reproduction of cancer cells. Cell cycle and related genes analyses showed that PTEN may play a key role in the process. In our studies, we found that Isoflavones could antagonize the DNA damage caused by cadmium. It may contribute to its anti-oxidative characteristic. Isoflavones may neutralize the reactive oxygen species caused by cadmium, and it is the important mechanism for isoflavones to prevent cancer.In summary, cadmium could induce DNA damage and further induce p53-independent rapid G2 checkpoint and p53-dependent delay G2 checkpoint. The DNA damage did not induce apoptosis but induce permanent cell cycle suspension, senescence and death. Some DNA damage cells enter the further cell cycle and the damaged DNA would enter offspring cells. That is an important mechanism for carcinogenicity of cadmium. However, isoflavones could prevent carcinogenicity of cadmium.
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