Molecular and Cellular Mechanisms of Hexavalent Chromium-Induced Lung Cancer: An Updated Perspective

Abstract

For over a century, chromium (Cr) has found widespread industrial and commercial use, namely as a pigment, in the production of stainless steel and in chrome plating. The adverse health effects to the skin and respiratory tract of prolonged exposure to Cr have been known or suspected for a long time, but it was much more recently that the toxicity of this element was unequivocally attributed to its hexavalent state. Based on the combined results of extensive epidemiological studies, animal carcinogenicity studies and several types of other relevant data, authoritative regulatory agencies have found sufficient evidence to classify hexavalent chromium [Cr(VI)] compounds as encountered in the chromate production, chromate pigment production and chromium plating industries as carcinogenic to humans. Crucial for the development of novel strategies to prevent, detect and/or treat Cr(VI)-induced cancers is a detailed knowledge of the molecular and cellular mechanisms underlying these pathologies. Unfortunately, in spite of a considerable research effort, crucial facets of these mechanisms remain essentially unknown. This review is intended to provide a concise, integrated and critical perspective of the current state of knowledge concerning multiple aspects of Cr(VI) carcinogenesis. It will present recent theories of Cr(VI)-induced carcinogenesis and will include aspects not traditionally covered in other reviews, such as the possible involvement of the energy metabolism in this process. A brief discussion on the models that have been used in the studies of Cr(VI)-induced carcinogenicity will also be included, due to the impact of this parameter on the relevance of the results obtained.

Short‐term exposure of nontumorigenic human bronchial epithelial cells to carcinogenic chromium(VI) compromises their respiratory capacity and alters their bioenergetic signature

“…These observations included changes in morphology and pattern of growth characteristic of an early phase of pre‐malignant progression [10] and overexpression of genes commonly involved in malignant transformation (e.g., MYC ) [40]. Yet, despite the combined efforts of many research groups, the molecular basis of Cr(VI) carcinogenicity remains elusive [49]. Namely, clarification is needed on the impact of Cr(VI) compounds on mammalian cell bioenergetics.…”

Intranasal Chromium Induces Acute Brain and Lung Injuries in Rats: Assessment of Different Potential Hazardous Effects of Environmental and Occupational Exposure to Chromium and Introduction of a Novel Pharmacological and Toxicological Animal Model

“…Moreover, environmental exposure to urban complex mixtures of particulate matter (PM) containing Cr has been stated as an undisputed risk factor for lung cancer [9, 10]. CrVI has been listed as a hazardous air pollutant (HAP) by the US Environmental Protection Agency (2004), as it is emitted from anthropogenic sources including industries, fuel combustion, and corrosion inhibition [11–13].…”

Hexavalent chromium, a lung carcinogen, confers resistance to thermal stress and interferes with heat shock protein expression in human bronchial epithelial cells

“…It is well established, though, that Cr(VI) is an inducer of oxidative, genotoxic and proteotoxic stress, through the generation of the above-mentioned reactive species, some of them potent oxidizers (Fornace et al 1981;Tsapakos and Wetterhahn 1983;Myers 2012;Urbano et al 2012;Li et al 2015). Cr(VI)induced deregulated cellular energetics, as shown by us (Rodrigues et al 2009;Goncalves et al 2011;Ferreira et al 2012;Cerveira et al 2014) and others (Liu et al 2010;Myers et al 2010;Molina-Jijon et al 2011;Xiao et al 2012a;Abreu et al 2014), likely constitutes an additional major stressor.…”