Trace elements and carcinogenicity: a subject in review

Cancer is known to be a multi-step process, which involves different stages including initiation, promotion, progression and metastasis. Chemical carcinogens including most trace elements can change any of these processes to induce their carcinogenic effects. Various studies confirm that cancer arises from the accumulation of irreversible DNA damage, which results from multiple mutations in critical genes in the body organ. Chemical carcinogens most often directly or after xenobiotic metabolism, act as genotoxic causes to induce DNA damage. Genotoxic carcinogen refers to a group of chemicals capable of producing cancer by directly altering the genetic material of target cells. Other carcinogens are however classified as non-genotoxic, which represents chemicals that are capable of producing cancer by some secondary mechanism not related to direct gene damage. They act as tumor promoters, endocrine-modifiers, receptor mediators, immunosuppressant, or inducers of tissue-specific toxicity and inflammatory responses. The diversity of modes of action, of non-genotoxic carcinogens, the tissue and species specificity and the absence of genotoxicity makes it extremely hard to predict their carcinogenic potential. The roles of trace metals (some of which are either genotoxic or non-genotoxic) in cancer development and inhibition have a complex character and have raised many questions because of their essential and toxic effects on people's health. Trace metals such as cadmium, nickel, arsenic, beryllium and chromium (VI) have been recognized as human or animal carcinogens by International Agency for Research on Cancer (IARC). The Carcinogenic capability of these metals depends mainly on factors such as oxidation states and chemical structures. The oxidative concept in metal carcinogenesis proposes that complexes formed by these metals, in vivo, in the vicinity of DNA, catalyze redox reactions, which in turn oxidize DNA. The most significant effect of reactive oxygen species in the carcinogenesis progression is DNA damage, which results in DNA lesions like strand breaks and the sister-chromatid exchange. This article reviews the carcinogenicity of various trace elements.