Oxidative Stress and Chromium(VI) Carcinogenesis

Abstract

Cr(VI)-containing compounds are known carcinogens that are present in industrial settings and in the environment. The biological mechanisms responsible for the initiation and pregression of diseases resulting from exposure to Cr(VI) are not fully understood. In the last two decades, there has been increasing evidence of the correlation between Cr(VI)-induced generation of reactive oxygen species and carcinogenic actions. This article summarizes the current literature on Cr(VI)-induced generation in various chemical and biological systems. This article also covers the relationship between Cr(VI)-induced oxidative stress and activation of transcription factors NF-kappaB, AP-1, p53, and hypoxia-inducible factor 1, regulation of cell cycle, and induction of apoptosis.

Chromium Inhibits in Vitro Viability and Steroidogenic in Ram Leydig Cells

“…Thus, the oxidative stress in the Leydig cells may be proposed after exposure to Cr (VI) appears to be due to poor scavenging of free radicals by the antioxidant enzymes through the direct deleterious effect of Cr. These results are supported by those of previous reports demonstrating that Cr (VI)-induced oxidative stress via the suppression of antioxidant enzymes plays a major role in male infertility (44). However, since Leydig cells are a terminally differentiated cell type, the lack of p53…”

“…The Chromium harmful effects may be exerted the second line through cellular reductants, potentially disruption intermediates; facilitated formation; oxygen, sulfur, and chromium radicals are generated (44). In a cell-free system, chromium (VI) high affinity with glutathione (Fenton-type reactions form hydroxyl) is formed Cr +5 as well as thiyl radicals under ascorbate (45).…”

Melatonin: A pleiotropic molecule regulating inflammation

“…ROS are involved in a variety of different cellular processes ranging from physiological to pathological responses. It is well known that ROS can promote cell survival, proliferation and differentiation at physiological levels, but also cell death by apoptosis or necrosis at higher levels [66]. Oxidative stress has a direct toxic Page 7 of 29 A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 -7 -effect on cells, which leads to lipid peroxidation, protein oxidation or DNA damage; it plays a causative or adjuvant role in almost all human pathologies, including cancer and neurodegeneration, and is involved in aging and chronic inflammatory pathologies.…”

Chromium induces chromosomal instability, which is partly due to deregulation of BubR1 and Emi1, two APC/C inhibitors

“…28,29 Cr(VI)-induced oxidative stress appears to perturb the activities of transcription factors, including NFκB, AP-1, p53 and HIF-1. 29 However, the molecular basis by which Cr(VI) causes deregulation of cell cycle checkpoints Figure 5. Cr(VI) reduces expression of emi1 and perturbs regulation of geminin and Cdt1.…”