• Effect of Cadmium on mutagenesis and DNA repair system
  • Aida Heidari,1,* Fatemeh Maghool,2
    1. Poursina Hakim Digestive Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
    2. Poursina Hakim Digestive Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran


  • Introduction: Cancer is a major medical and public health issue affecting millions worldwide. Both genetic and environmental factors are involved in the etiology of cancer. Hereditary nonpolyposis colorectal cancer (HNPCC), which is characterized by the development of several cancers such as colorectal, and endometrial cancer, is an autosomal dominant disorder caused by mismatch repair gene (MMR) mutations. DNA mismatch repair plays a key role in maintaining genomic stability by repairing DNA mismatched base pairs generated during DNA replication and recombination. Exposure to heavy metals is one of the potential environmental risk factors and multiple studies show an association between exposure to heavy metals and cancer. Cadmium is a kind of heavy metals which affecting human health through occupational and environmental exposure. Following chronic exposure, cadmium is able to produce malignant tumors in various organs. In this review, we will discuss the genotoxic and mutagenic effects of this carcinogenic metal.
  • Methods: Recently published articles (2010–2019) were searched in three electronic databases (MEDLINE, EMBASE, Cochrane Library) for relevant articles. Only English published articles were included.
  • Results: Available evidences suggest that cadmium exposure induces genomic instability through multiple mechanisms. Cadmium induces the increased generation of reactive oxygen species (ROS), which induce DNA damage. Other pathways that cadmium may interact with are DNA repair mechanisms, epigenetic mechanisms, as well as apoptosis. Cadmium inhibits the repair of all kinds of mismatches by interfering with main DNA repair pathways such as mismatch repair, base excision repair, and nucleotide excision repair, which may contribute to the initiation of tumor. In vitro studies also showed that cadmium blocks DNA binding and ATPase activities of MSH2–MSH6 heterodimer through the binding to specific sites on it. Accumulation of damaged DNA due to incapability to repair DNA damage contributes to mutation and carcinogenesis. Furthermore, Cadmium as a metabolic antagonist of zinc, a trace element involved in repair of DNA and genome stability, can substitute for zinc in Zn-dependent enzymes in the DNA repair process.
  • Conclusion: Interactions between genetic and environmental factors are complex and understanding them requires long term animal studies combined with exposure to other environmental pollutants as well as other disorders that proved to be associated with genomic instability. It will provide insight into the etiology and susceptibilities of cancer, and possibly permitting the prevention of that.
  • Keywords: DNA mismatch repair, heavy metals, cancer, cadmium