Molecular Mechanisms of Hexavalent Chromium–Induced Apoptosis in Human Bronchoalveolar Cells

Abstract

Hexavalent chromium (Cr[VI]) is classified by the International Agency for Research on Cancer as a group I carcinogen. Although the U.S. Occupational Safety and Health Administration was obliged to reduce the permissible exposure limit (PEL), it was reported that U.S. workers continue to be exposed to dangerously high Cr(VI) levels. In this study, we examined the role of p53 and target genes in a bronchoalveolar carcinoma isogenic cell line system and in primary human bronchial epithelial cells. p53-Negative parental H358 cell line, the same line in which the wild-type p53 expression vector (pC53-SN3) was introduced, and cells obtained from biopsies of human bronchus were exposed to chromate. Induction of DNA strand breaks were evaluated by alkaline elution assay, and apoptosis was analyzed by gel ladder, annexin V-PI staining, and ELISA, whereas p53 and target genes were evaluated by Western blots. Although Cr(VI) induced DNA strand breaks in both H358 cell clones, apoptosis was present only in the p53-transfected cells (H358p53(+/+)). In these cells, Cr(VI)-induced apoptosis is mediated by p53 upregulation of p53-upregulated modulator of apoptosis (PUMA), BAX translocation to mitochondria, cytochrome c release, and caspase-3 activation. In primary human bronchial epithelial cells expressing functional p53, Cr(VI) induced expression of PUMA and Noxa, which promote apoptosis through BAX. This result establishes p53 as the "necessary" player in Cr(VI)-induced apoptosis. To the best of our knowledge, this is the first report indicating strict correlation of Cr(VI) apoptosis to PUMA induction on primary human bronchoalveolar cells in short-term cultures.

Effect of chromium and cobalt ions on primary human lymphocytesin vitro

“…Therefore, it is likely that the cells are becoming apoptotic and unable to divide further rather than any direct impedance of cell activation and proliferation. Cr ions have been shown to induce apoptosis in lung epithelial cells (Russo et al, 2005) and fibroblasts (Carlisle et al, 2000) as well as in lymphocytes (Vasant et al, 2003) and macrophages ). Cr 6+ is known to stimulate a number of extrinsic and intrinsic apoptotic pathways (Sargeant and Goswami, 2007).…”

Risk of lung cancer according to mild steel and stainless steel welding

“…The latter is a well-established lung carcinogen (3,(13)(14)(15)(16). Manual metal arc (MMA) mild steel welders are, in general, more exposed to welding fumes than metal active gas (MAG), metal inert gas (MIG), and tungsten inert gas (TIG) welders, and most metal workers use more than one method during their worklife.…”

Chromium Inhibits in Vitro Viability and Steroidogenic in Ram Leydig Cells

“…Intracellularly led to promote the formation of complex "DNA-phosphate-based" adducts that reason a variety of direct genomic impairments and lost their belonging to testosterone (34).…”