Effects of Cr(VI) on the expression of the oxidative stress genes in human lung cells.
Intracellular metabolism of chromium(VI) [Cr(VI)] may lead to oxidative stress and this may account for the ability of Cr(VI) to act as a complete carcinogen. Therefore, we examined the effects of Cr(VI) treatment on the expression of oxidative stress genes in normal human lung LL 24 cells and human lung adenocarcinoma A549 cells. RT-PCR and northern blot analyses were used to determine the steady-state mRNA levels of catalase, glutathione S-transferase, glutathione reductase, Cu/Zn- and Mn-superoxide dismutases, glutathione peroxidase, NAD(P)H:quinone oxidoreductase, heme oxygenase and interleukin 8 in control cells and cells treated with 5-200 microM of Cr(VI). We found that only expression of the heme oxygenase gene is strongly elevated under the treatment with Cr(VI), and only in normal human lung LL 24 cells. Our data showed that even in the absence of Cr(VI) treatment, the level of heme oxygenase gene expression is much higher in A549 cells than in LL 24 cells. As glutathione is believed to play a protective role in cells against different forms of oxidative stress, we studied the correlation between intracellular glutathione levels and the inducibility of the heme oxygenase gene after treatment of cells with Cr(VI). Our results demonstrate that glutathione levels are increased by 35 % of control values in LL 24 cells treated with Cr(VI). The data obtained indicate that heme oxygenase, known to be a stress-inducible gene, may be involved in cellular pathways critical to the carcinogenic activity of Cr(VI) in normal human lung cells. Intracellular glutathione levels and reactive oxygen species do not appear to be primarily responsible for the stress response, induced by Cr(VI) in the studied human cells.
Dubrovskaya
V A
VA
Department of Chemistry, Dartmouth College, Hanover, NH 03755-3564, USA.
Wetterhahn
K E
KE
D000111:Acetylcysteine / Q000494:pharmacology; D000199:Actins / Q000378:metabolism*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002460:Cell Line / Q000187:drug effects; D002857:Chromium / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000199:Actins; D002274:Carcinogens, Environmental; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D002857:Chromium; C074702:chromium hexavalent ion; D006419:Heme Oxygenase (Decyclizing); D013482:Superoxide Dismutase; D005978:Glutathione; D000111:Acetylcysteine