Chemical Models Important in Understanding the Ways in Which Chromate Can Damage DNA

Abstract

Chromate is an established human carcinogen. There have been many studies of the reactivity of chromate aimed at improving understanding of chromate toxicity. In the present paper a number of conclusions of these studies are reviewed and considered in the light of new results obtained in our laboratories. A number of hypotheses are considered; it is concluded, however, that it is impossible to reconcile the generation of strand breaks by chromate during its reduction by glutathione with any simple mechanism involving the generation of DNA lesions by free hydroxyl radicals. Kinetic, spin-trapping, and competition kinetic studies, based on a strand-breaking assay, are reported in support of this conclusion. -Environ Health Perspect 1 02(Suppl 3):3-10 (1994).

Protective effect of SnCl2 on K2Cr2O7-induced nephrotoxicity in rats: The indispensability of HO-1 preinduction and lack of association with some antioxidant enzymes

“…Evidences suggest that ROS are involved in Cr(VI)-induced cell injury (Bagchi et al, 2002;Liu and Shi, 2001;Sengupta et al, 1992;Stohs and Bagchi, 1995). Chromium reduction intermediates [Cr(V), Cr(IV), and Cr(III)], which may be generated during physiological conditions, may be toxic as they involve ROS production (O' Brien and Kortenkamp, 1994;Shi and Dalal, 1994;Stohs et al, 2000). In vitro chromate reduction via hydrogen peroxide has been shown to produce hydroxyl radicals via a Fenton-like reaction (Aiyar et al, 1991;Liu et al, 1997;O'Brien and Kortenkamp, 1994;Shi and Dalal, 1990;Tsou et al, 1996).…”

Time course study of oxidative and nitrosative stress and antioxidant enzymes in K2Cr2O7-induced nephrotoxicity

“…Evidences suggest that reactive oxygen species (ROS) are involved in Cr(VI)-induced cell injury [16,17,19,26]. Chromium reduction intermediates [Cr(V), Cr(IV), and Cr(III)], which could be generated under physiological conditions, may be toxic as they involve ROS production [27-29]. In vitro chromate reduction via H 2 O 2 has been shown to produce hydroxyl radicals via a Fenton-like reaction [27,30-33].…”

Metal toxicity in two rodent species and redox potential: Evaluation of quantitative structure—activity relationships

“…Free radicals may be generated when these metal ions acquire electrons from donor species, such as oxygen, to form highly reactive oxygen radicals, although a number of possibilities exist for potential oxygen radical species, for example, the superoxide anion and the hydroxyl radical. Substantial evidence exists for the association between generation of reactive oxygen species and various forms of toxicity [35‐ 37], including those induced by metal compounds [38,39], the variation in acute toxicity for the metals under consideration may be due to their ability to produce reactive oxygen species. In addition to direct combination with molecular oxygen, the possibility of hydroxyl radical generation [40] also occurs when the metal ion reacts with water, according to the following equation: where M n+ and M (n ‐ 1)+ represent two different redox states of the metal concerned and, consequently, this would apply to metals that are capable of existing in more than one oxidation state, such as those of the transition series.…”