Abstract
Well-documented evidence suggests that environmental and occupational exposure of toxic metals or metal-containing compounds can cause a number of human diseases, including inflammation and cancer, through DNA damage, protein modifications, or lipid peroxidation. This mini-review addresses the mechanisms of cell death induced by some carcinogenic metals, including arsenic (III), chromium (VI) and vanadium (V). A possible contribution of reactive oxygen species to metal-induced cell death is also discussed.
Similar content being viewed by others
References
Green DR, Reed JC: Mitochondria and apoptosis. Science 281: 1309–1312, 1998
Ashkenazi A, Dixit VM: Death receptors: Signaling and modulation. Science 281: 1305–1308, 1998
LaCasse EC, Baird S, Korneluk RG, MacKenzie AE: The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene 17: 3247–3259, 1998
Reed JC: Bcl-2 family proteins. Oncogene 17: 3225–3236, 1998
Beckman KB, Ames BN: Mitochondrial aging: Open questions. Ann NY Acad Sci 854: 118–127, 1998
De Laurenzi V, Melino G: Apoptosis. The little devil of death. Nature 406: 135–136, 2000
Du C, Fang M, Li Y, Li L, Wang X: Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102: 33–42, 2000
Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE, Moritz RL, Simpson RJ, Vaux DL: Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 102: 43–53, 2000
Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM, Kroemer G: Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397: 441–446, 1999
Blankenship LJ, Manning FC, Orenstein JM, Patierno SR: Apoptosis is the mode of cell death caused by carcinogenic chromium. Toxicol Appl Pharmacol 126: 75–83, 1994
Manning FC, Blankenship LJ, Wise JP, Xu J, Bridgewater LC, Patierno SR: Induction of internucleosomal DNA fragmentation by carcinogenic chromate: Relationship to DNA damage, genotoxicity, and inhibition of macromolecular synthesis. Environ Health Perspect 102 (suppl 3): 159–167, 1994
Singh J, McLean JA, Pritchard DE, Montaser A, Patierno SR: Sensitive quantitation of chromium-DNA adducts by inductively coupled plasma mass spectrometry with a direct injection high-efficiency nebulizer. Toxicol Sci 46: 260–265, 1998
Hamilton JW, Kaltreider RC, Bajenova OV, Ihnat MA, McCaffrey J, Turpie BW, Rowell EE, Oh J, Nemeth MJ, Pesce CA, Lariviere JP: Molecular basis for effects of carcinogenic heavy metals on inducible gene expression. Environ Health Perspect 106 (suppl 4): 1005–1015, 1998
Shi X, Leonard SS, Wang S, Ding M: Antioxidant properties of pyrrolidine dithiocarbamate and its protection against Cr (VI)-induced DNA strand breakage. Ann Clin Lab Sci 30: 209–216, 2000
Wang S, Leonard SS, Ye J, Ding M, Shi X: The role of hydroxyl radical as a messenger in Cr (VI)-induced p53 activation. Am J Physiol Cell Physiol 279: C868–875, 2000
Carlisle DL, Pritchard DE, Singh J, Patierno SR: Chromium (VI) induces p53-dependent apoptosis in diploid human lung and mouse dermal fibroblasts. Mol Carcinog 28: 111–118, 2000
Jimenez GS, Khan SH, Stommel JM, Wahl GM: p53 regulation by post-translational modification and nuclear retention in response to diverse stresses. Oncogene 18: 7656–7665, 1999
Ashcroft M, Kubbutat MH, Vousden KH: Regulation of p53 function and stability by phosphorylation. Mol Cell Biol 19: 1751–1758, 1999
Milne DM, Campbell DG, Caudwell FB, Meek DW: Phosphorylation of the tumor suppressor protein p53 by mitogen-activated protein kinases. J Biol Chem 269: 9253–9260, 1994
Milne DM, Campbell LE, Campbell DG, Meek DW: p53 is phosphorylated in vitro and in vivo by an ultraviolet radiation-induced protein kinase characteristic of the c-Jun kinase, JNK1. J Biol Chem 270: 5511–5518, 1995
Chen F, Ding M, Lu Y, Leonard SS, Vallyathan V, Castranova V, Shi X: Participation of MAP kinase p38 and IkappaB kinase in chromium (VI)-induced NF-kappaB and AP-1 activation. J Environ Pathol Toxicol Oncol 19: 231–238, 2000
Hainaut P, Milner J: Redox modulation of p53 conformation and sequence-specific DNA binding in vitro. Cancer Res 53: 4469–4473, 1993
Meplan C, Richard MJ, Hainaut P: Redox signalling and transition metals in the control of the p53 pathway. Biochem Pharmacol 59: 25–33, 2000
Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B: A model for p53-induced apoptosis. Nature 389: 300–305, 1997
Amundson SA, Myers TG, Fornace AJ Jr: Roles for p53 in growth arrest and apoptosis: Putting on the brakes after genotoxic stress. Oncogene 17: 3287–3299, 1998
Gu Z, Flemington C, Chittenden T, Zambetti GP: ei24, a p53 response gene involved in growth suppression and apoptosis. Mol Cell Biol 20: 233–241, 2000
Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N: Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288: 1053–1058, 2000
Shi XL, Dalal NS: The role of superoxide radical in chromium (VI)-generated hydroxyl radical: The Cr (VI) Haber-Weiss cycle. Arch Biochem Biophys 292: 323–327, 1992
Stohs SJ, Bagchi D, Hassoun E, Bagchi M: Oxidative mechanisms in the toxicity of chromium and cadmium ions. J Environ Pathol Toxicol Oncol 19: 201–213, 2000
Buzard GS, Kasprzak KS: Possible roles of nitric oxide and redox cell signaling in metal-induced toxicity and carcinogenesis: A review. J Environ Pathol Toxicol Oncol 19: 179–199, 2000
Carlisle DL, Pritchard DE, Singh J, Owens BM, Blankenship LJ, Orenstein JM, Patierno SR: Apoptosis and p53 induction in human lung fibroblasts exposed to chromium (VI): Effect of ascorbate and tocopherol. Toxicol Sci 55: 60–68, 2000
Iyengar GV, Nair PP: Global outlook on nutrition and the environment: Meeting the challenges of the next millennium. Sci Total Environ 249: 331–346, 2000
Simeonova PP, Wang S, Toriuma W, Kommineni V, Matheson J, Unimye N, Kayama F, Harki D, Ding M, Vallyathan V, Luster MI: Arsenic mediates cell proliferation and gene expression in the bladder epithelium: Association with activating protein-1 transactivation. Cancer Res 60: 3445–3453, 2000
Chen GQ, Zhu J, Shi XG, Ni JH, Zhong HJ, Si GY, Jin XL, Tang W, Li XS, Xong SM, Shen ZX, Sun GL, Ma J, Zhang P, Zhang TD, Gazin C, Naoe T, Chen SJ, Wang ZY, Chen Z: In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood 88: 1052–1061, 1996
Cai X, Shen YL, Zhu Q, Jia PM, Yu Y, Zhou L, Huang Y, Zhang JW, Xiong SM, Chen SJ, Wang ZY, Chen Z, Chen GQ: Arsenic trioxideinduced apoptosis and differentiation are associated respectively with mitochondrial transmembrane potential collapse and retinoic acid signaling pathways in acute promyelocytic leukemia. Leukemia 14: 262–270, 2000
Larochette N, Decaudin D, Jacotot E, Brenner C, Marzo I, Susin SA, Zamzami N, Xie Z, Reed J, Kroemer G: Arsenite induces apoptosis via a direct effect on the mitochondrial permeability transition pore. Exp Cell Res 249: 413–421, 1999
Huang C, Ma WY, Li J, Dong Z: Arsenic induces apoptosis through a c-Jun NH2-terminal kinase-dependent, p53-independent pathway. Cancer Res 59: 3053–3058, 1999
Wang TS, Kuo CF, Jan KY, Huang H: Arsenite induces apoptosis in Chinese hamster ovary cells by generation of reactive oxygen species. J Cell Physiol 169: 256–268, 1996
Chen YC, Lin-Shiau SY, Lin JK: Involvement of reactive oxygen species and caspase 3 activation in arsenite-induced apoptosis. J Cell Physiol 177: 324–333, 1998
Chen NY, Ma WY, Yang CS, Dong Z: Inhibition of arsenite-induced apoptosis and AP-1 activity by epigallocatechin-3-gallate and theaflavins. J Environ Pathol Toxicol Oncol 19: 287–295, 2000
Bauer MKA, Vogt M, Los M, Siegel J, Wesselborg S, Schulze-Osthoff K: Role of reactive oxygen intermediates in activation-induced CD95 (APO-1/Fas) ligand expression. J Biol Chem 273: 8048–8055, 1998
Vogt M, Bauer MK, Ferrari D, Schulze-Osthoff K: Oxidative stress and hypoxia/reoxygenation trigger CD95 (APO-1/Fas) ligand expression in microglial cells. FEBS Lett 429: 67–72, 1998
Hug H, Strand S, Grambihler A, Galle J, Hack V, Stremmel W, Krammer PH, Galle PR: Reactive oxygen intermediates are involved in the induction of CD95 ligand mRNA expression by cytostatic drugs in hepatoma cells. J Biol Chem 272: 28191–28193, 1997
Bossy-Wetzel E, Newmeyer DD, Green DR: Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD-specific caspase activation and independently of mitochondrial transmembrane depolarization. Embo J 17: 37–49, 1998
Bessho R, Matsubara K, Kubota M, Kuwakado K, Hirota H, Wakazono Y, Lin YW, Okuda A, Kawai M, Nishikomori R, Heike T: Pyrrolidine dithiocarbamate, a potent inhibitor of nuclear factor kappa B (NF-kappa B) activation, prevents apoptosis in human promyelocytic leukemia HL-60 cells and thymocytes. Biochem Pharmacol 48: 1883–1889, 1994
Chen F, Lu Y, Zhang Z, Vallyathan V, Ding M, Castranova V, Shi X: Opposite effect of NF-kB and c-Jun-N-terminal kinase on p53-independent GADD45 induction by arsenite. J Biol Chem 276: 11414–11419, 2001
Barceloux DG: Vanadium. J Toxicol Clin Toxicol 37: 265–278, 1999
Afshari CA, Kodama S, Bivins HM, Willard TB, Fujiki H, Barrett JC: Induction of neoplastic progression in Syrian hamster embryo cells treated with protein phosphatase inhibitors. Cancer Res 53: 1777–1782, 1993
Sabbioni E, Pozzi G, Devos S, Pintar A, Casella L, Fischbach M: The intensity of vanadium (V)-induced cytotoxicity and morphological transformation in BALB/3T3 cells is dependent on glutathione-mediated bioreduction to vanadium (IV). Carcinogenesis 14: 2565–2568, 1993
Hehner SP, Hofmann TG, Droge W, Schmitz ML: Inhibition of tyrosine phosphatases induces apoptosis independent from the CD95 system. Cell Death Differ 6: 833–841, 1999
Huang C, Zhang Z, Ding M, Li J, Ye J, Leonard SS, Shen HM, Butterworth L, Lu Y, Costa M, Rojanasakul Y, Castranova V, Vallyathan V, Shi X: Vanadate induces p53 transactivation through hydrogen peroxide and causes apoptosis. J Biol Chem 275: 32516–32522, 2000
Chin LS, Murray SF, Harter DH, Doherty PF, Singh SK: Sodium vanadate inhibits apoptosis in malignant glioma cells: A role for Akt/PKB. J Biomed Sci 6: 213–218, 1999
Scheving LA, Thomas JR, Zhang L: Regulation of intestinal tyrosine phosphorylation and programmed cell death by peroxovanadate. Am J Physiol 277: C572–579, 1999
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chen, F., Vallyathan, V., Castranova, V. et al. Cell apoptosis induced by carcinogenic metals. Mol Cell Biochem 222, 183–188 (2001). https://doi.org/10.1023/A:1017970330982
Issue Date:
DOI: https://doi.org/10.1023/A:1017970330982