Interactions between chromium species and DNA in vitro and their potential role in the toxicity of hexavalent chromium

Epidemiological and animal studies have supported the carcinogenicity of hexavalent chromium [Cr(VI)]; however, molecular changes responsible for the induction of cancer by Cr(VI) are not entirely understood. Numerous mechanistic studies suggested the role of oxidative stress and genotoxicity in Cr(VI)-mediated carcinogenesis; however, specific types of DNA damage have not yet been conclusively attributed to specific chromium species or other reactive byproducts generated in biological systems exposed to Cr(VI). Due to the remarkably complex chemistry and biological effects of chromium species generated through the intracellular reduction of Cr(VI), their relevance for Cr(VI)-mediated carcinogenesis has not yet been fully elucidated and continues to be a subject of ongoing discussions in the field. In this report, we describe a complex world of chromium species and their reactivity with DNA and other biologically relevant molecules in vitro to inform a more complete understanding of Cr(VI)-mediated toxicity. In addition, we discuss previous results in the context of in vitro models and analytical methods to reconcile some conflicting findings on the biological role of chromium species.

Automated summary

Epidemiological and animal studies have supported the carcinogenicity of hexavalent chromium (Cr(VI)) but the specific molecular changes responsible for this induction of cancer are still not fully understood. The role of oxidative stress and genotoxicity in Cr(VI)-mediated carcinogenesis has been suggested, but the specific types of DNA damage attributed to specific chromium species or other reactive byproducts in biological systems exposed to Cr(VI) have not been definitively determined. The complexity of chromium species and their reactivity with DNA and other biologically relevant molecules in vitro is discussed in this report to provide a more comprehensive understanding of Cr(VI)-mediated toxicity and to reconcile conflicting findings on the biological role of chromium species in previous studies.