Mechanisms of Cadmium Carcinogenicity in the Gastrointestinal Tract


Cancer, a serious public health problem in worldwide, results from an excessive and uncontrolled proliferationof the body cells without obvious physiological demands of organs. The gastrointestinal tract, including theesophagus, stomach and intestine, is a unique organ system. It has the highest cancer incidence and cancerrelatedmortality in the body and is influenceed by both genetic and environmental factors. Among the variouschemical elements recognized in the nature, some of them including zinc, iron, cobalt, and copper have essentialroles in the various biochemical and physiological processes, but only at low levels and others such as cadmium,lead, mercury, arsenic, and nickel are considered as threats for human health especially with chronic exposureat high levels. Cadmium, an environment contaminant, cannot be destroyed in nature. Through impairmentof vitamin D metabolism in the kidney it causes nephrotoxicity and subsequently bone metabolism impairmentand fragility. The major mechanisms involved in cadmium carcinogenesis could be related to the suppression ofgene expression, inhibition of DNA damage repair, inhibition of apoptosis, and induction of oxidative stress. Inaddition, cadmium may act through aberrant DNA methylation. Cadmium affects multiple cellular processes,including signal transduction pathways, cell proliferation, differentiation, and apoptosis. Down-regulation ofmethyltransferases enzymes and reduction of DNA methylation have been stated as epigenetic effects of cadmium.Furthermore, increasing intracellular free calcium ion levels induces neuronal apoptosis in addition to otherdeleterious influence on the stability of the genome.