African Journal of Biotechnology Vol. 5 (1), pp. 001-014, 2 January 2006          
ISSN 1684–5315 © 2006 Academic Journals

Review

Aflatoxin contamination of foods in developing countries: Implications for hepatocellular carcinoma and chemopreventive strategies

E. Olatunde Farombi*

Drug Metabolism and Toxicology Unit, Department of Biochemistry, College of Medicine, University of Ibadan Nigeria. Fax: 234-2-8103043. Tel: 234-8023470333. E-mail: olatunde_farombi@yahoo.com or ofarombi@skannet.com.

*On Sabbatical Leave at the National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.

Accepted 29 December, 2005

Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer mortality in the world and, in certain parts of Asia and Africa, it accounts for about 70% of cancer deaths. Chronic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin B­₁ (AFB₁) are the two major risk factors in multi factorial aetiology of HCC. Multiple lines of evidence indicate synergistic interaction between these two agents in the development of HCC. Several mechanisms of interaction have been suggested including activation of cytochrome P450s by HBV infection leading to the metabolism of inactive AFB₁ to the mutagenic AFB₁-8,9-epoxide as well as the generation of reactive oxygen species by HBV and AFB₁ sensitising the cells to AFB₁-induced p53 249^ser mutations. The poor survival rate achieved by the current surgical procedures and chemotherapy treatment has motivated a number of scientific investigations to elucidating the molecular events involved in HCC thus providing the scientific rationale for prevention strategies, including primary and chemoprevention approaches. Recent findings have implicated intracellular signalling cascades involving nuclear factor kappa B (NF-kB) and nuclear transcription factor erythroid 2p45 (NF-E2)-related factor 2 (Nrf2) as molecular targets of a wide range of chemopreventive agents. The new findings thus raise the intriguing possibility that chemopreventives modulating these molecular targets in the liver might provide a novel therapeutic approach to the development of liver cancer.

Key words: Hepatocellular carcinoma, chronic hepatitis B virus, aflatoxin B­₁, chemoprevention.