Carcinogenesis arsenic

Exposure to arsenic has been associated with different types of human cancers such as respiratory cancers and epidermoid carcinomas of the skin, as well as precancerous dermal keratosis. The epidemiological evidence of human carcinogenicity is supported by carcinogenesis in experimental animals (Deknudt et al. 1986). 

Lee, T.C., M. Oshimura, and J.C. Barrett. 1985. Comparison of arsenic-induced cell transformation, cytotoxicity, mutation and cytogenetic effects in Syrian hamster embryo cells in culture. Carcinogenesis 6 1421-1426. 

Yu, H.-S. et al., Alterations of skin-associated tissue lymphoid tissue in the carcinogenesis of arsenical skin cancer, Proc. Natl. Sci. Counc. Repub. China B, 16, 17, 1992. 

Simeonova, P. P. et al., c-Src-dependent activation of the epidermal growth factor receptor and mitogen-activated protein kinase pathway by arsenic. Role in carcinogenesis, J. Biol. Chem., 277, 2945, 2002. 

Hamadeh, H. K. et al., Arsenic disrupts cellular levels of p53 and mdm2 A potential mechanism of carcinogenesis, Biochem. Biophys. Res. Commun., 263, 446, 1999. 

Matsui, M. et al., The role of oxidative DNA damage in human arsenic carcinogenesis Detection of 8-hydroxy-2 -deoxyguanosine in arsenic-related Bowen s disease, J. Invest. Dermatol., 113, 26, 1999. 

This research is an outgrowth of an earlier project which sought to characterize the mechanism of arsenic metabolism in a population currently drinking arsenic-contaminated water in Taiwan. There were three parts to the study, a cohort study, a case control study for skin cancer, and a study of intra-individual variability associated with chronic arsenic exposure. The latter three research projects are complete and being submitted for publication. The results of this research are highly relevant since they indicate that alterations in methylation capacity may affect arsenic carcinogenesis. 

Just within the past decade have definitive animal studies for arsenic-induced carcinogenesis emerged with positive results (Kitchin, 2001 Hughes, 2002 Rossman, 2003 Wanibuchi et al., 2004 Cohen et al., 2006 Waalkes, Liu and Diwan, 2007). Up until this point, standard lifetime cancer bioassays with inorganic... 

Burns, F.J., Uddin, A.N., Wu, F. et al. (2004) Arsenic-induced enhancement of ultraviolet radiation carcinogenesis in mouse skin a dose-response study. Environmental Health Perspectives, 112(5), 599-603. 

Hartwig, A., Groblinghoff, U.D., Beyersmann, D. et al. (1997) Interaction of arsenic(III) with nucleotide excision repair in UV-irradiated human fibroblasts. Carcinogenesis, 18(2), 399-405. 

Hughes, M.F. and Kitchin, K.T. (2006) Arsenic, oxidative stress and carcinogenesis, in Oxidative Stress, Disease and Cancer (ed. K.K. Singh), Imperial College Press, London, pp. 825-50. 

Kitchin, K.T. (2001) Recent advances in arsenic carcinogenesis modes of action, animal model systems, and methylated arsenic metabolites. Toxicology and Applied Pharmacology, 172(3), 249-61. 

Mass, M.J. and Wang, L. (1997) Arsenic alters cytosine methylation patterns of the promoter of the tumor suppressor gene p53 in human lung cells a model for a mechanism of carcinogenesis. Mutation Research-Reviews in Mutation Research, 386(3), 263-77. 

Rossman, T.G. (2003) Mechanism of arsenic carcinogenesis an integrated approach. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 533(1-2), 37-65. 

Rossman, T.G., Uddin, A.N., Burns, F.J. and Bosland, M.C. (2001) Arsenite is a cocarcinogen with solar ultraviolet radiation for mouse skin an animal model for arsenic carcinogenesis. Toxicology and Applied Pharmacology, 176(1), 64-71. 

Tseng, C.-H. (2005) Blackfoot disease and arsenic A never-ending story. Journal of Environmental Science and Health-Part C Environmental Carcinogenesis and Ecotoxicology Reviews, 23(1), 55-74. 

Yamanaka, K., Takabayashi, F., Mizoi, M. et al. (2001) Oral exposure of dimethylarsinic acid, a main metabolite of inorganic arsenics, in mice leads to an increase in 8-oxo-2 -deoxyguanosine level, specifically in the target organs for arsenic carcinogenesis. Biochemical and Biophysical Research Communications, 287(1), 66-70. 

Carcinogenicity. A number of metals have been shown to be carcinogenic in humans or animals. Arsenic, certain chromium compounds, and nickel are known human carcinogens beryllium, cadmium, and cisplatin are probable human carcinogens. The carcinogenic action, in some cases, is thought to result from the interaction of the metallic ions with DNA (see Chapter 11 for a detailed discussion of carcinogenesis). 

The data concerning dietary exposure to iron, zinc, copper, molybdenum, iodine, arsenic, cadmium, and lead are insufficient and provide no basis for conclusions about the association of these elements with carcinogenesis. 

M.J. Mass, Human carcinogenesis by arsenic. Environ. Geochem. Health 14 49,... 

E. Sabbioni, M. Fischbach, G. Pozzi, R. Pietra, M. Gallorini, J. L. Piette, Cellular retention, toxicity and carcinogenic potential of seafood arsenic. 1. Lack of cytotoxicity and transforming activity of arsenobetaine in the BALB/3T3 cell line, Carcinogenesis, 12 (1991), 1287-1291. 

S. Yamamoto, Y. Konishi, T. Murai, M. A. Shibata, T. Matsuda, K. Kuroda, G. Endo, S. Fukushima, Enhancing effects of an organic arsenic compound dimethy-larsenic (cacodylic acid) in a multi-organism carcinogenesis bioassay, Appl. Organomet. Chem., 8 (1994), 197-201. 

Brown, J., Kitchin, K., George, M. Dimethylarsinic acid treatment alters six different rat biochemical parameters relevance to arsenic carcinogenesis. Teratog. Carcinog. Mutagen. 17, 71-84 (1997)... 

Kato, K., Yamanaka, K., Nakano, M., Hasegawa, A., Okada, S. (2000). 72-kDa stress protein (hsp72) induced by administration of dimethylarsinic acid to mice accumulates in alveolar flat cells of lung, a target organ for arsenic carcinogenesis. Biol. Pharm. Bull. 23 1212-15. 

Carcinogenesis Studies (Feed) Equivocal Evidence rat NTPTR NTP-TR-345,89 (Feed) No Evidence mouse NTPTR NTP-TR-345,89. Arsenic and its compounds are on the Community Right-To-Know List. Reported in EPA TSCA Inventory. 

One area that is of interest and will not be covered in this review is the carcinogenesis, mutagenesis, teratology of arsenic. There have been a considerable number of studies and the exact mechanism is not understood . However, it is known that exposure over a long period of time will cause mutagenesis and carcinogenesis and it has been thought to result from the inhibition of DNA repair. A number of the articles cited are review articles. 

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