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• Kakehashi, A
• Wei, M
• Fukushima, S
• Wanibuchi, H
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• Kakehashi, A
• Wei, M
• Fukushima, S
• Wanibuchi, H
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• Kakehashi, A
• Wei, M
• Fukushima, S
• Wanibuchi, H

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Cancers 2013, 5(4), 1332-1354; doi:10.3390/cancers5041332

Review

Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

Anna Kakehashi ¹, Min Wei ¹, Shoji Fukushima ² and Hideki Wanibuchi ^1,*

¹ Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585, Japan ² Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015, Japan

* Author to whom correspondence should be addressed.

Received: 16 August 2013; in revised form: 26 September 2013 / Accepted: 12 October 2013 / Published: 28 October 2013

(This article belongs to the Special Issue Role of Oxidatively-Induced DNA Damage in Carcinogenesis)

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Abstract: This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P₄₅₀ inducers, such as phenobarbital, a-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

Keywords: oxidative stress; carcinogenicity; chemical carcinogen; low dose

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