IngentaConnect Cigarette Smoking, Metabolic Activation and Carcinogenesis

Authors: Akiyoshi Nishikawa¹; Yukio Mori¹; In-Seon Lee¹; Takuji Tanaka¹; Masao Hirose¹

Source: Current Drug Metabolism, Volume 5, Number 5, October 2004 , pp. 363-373(11)

Publisher: Bentham Science Publishers

Abstract:

Epidemiologically, it has been suggested that cigarette smoking is closely associated with an increased risk of cancers in various organs such as the lung, oropharynx, stomach, pancreas, liver and colon. Nevertheless, influences of cigarette smoking on experimental tumorigenesis in organs other than the respiratory tract remain to be elucidated. In our experimental studies, it has been shown that cigarette smoke exposure induces hepatic CYP enzymes, especially CYP1A2, in both rats and hamsters, and S9 fraction from their livers exposed to cigarette smoke specifically increases the mutagenicity in Ames assay of various heterocyclic amines (HCAs) contained in cigarette smoke and cooked food, which is in good agreement with the fact that HCAs are principally activated by CYP1A2 to proximate carcinogens. In fact, cigarette smoke exposure enhanced liver carcinogenesis in rats induced by 2-amino-3, 8-dimethylimidazo[4, 5- f]quinoxaline (MeIQx), a major HCA. Furthermore, in our recent study, it was also shown that cigarette smoke exposure induces hepatic CYP2A8 in hamsters, which is homologous to CYP2A6 in human, and hepatic S9 fraction exposed to cigarette smoke increases the mutagenicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK), a tobacco specific nitrosamine, which is in line with the fact that NNK is metabolically activated by CYP2A6. Keeping these data, the aim of this review is to discuss any relevancy of modulated metabolic activation by cigarette smoking to cancer risk in human.

Keywords: Carcinogenesis; methylnitrosamino; butanone; pyridyl; CYP2A8

Document Type: Review article

DOI: 10.2174/1389200043335441

Affiliations: 1: Division of Pathology, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan.

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