Demonstration of ethanol-induced protein adducts in oral leukoplakia (pre-cancer) and cancer

Demonstration of ethanol-induced protein adducts in oral leukoplakia (pre-cancer) and cancer
Published article online:
04 Aug 2007
Accepted for publication June 26, 2007
To cite this article: Saman Warnakulasuriya, Seppo Parkkila, Toru Nagao, Victor R. Preedy, Markku Pasanen, Heidi Koivisto, Onni Niemelâ
Demonstration of ethanol-induced protein adducts in oral leukoplakia (pre-cancer) and cancer
Journal of Oral Pathology & Medicine (OnlineEarly Articles).
doi:10.1111/j.1600-0714.2007.00605.x
Blackwell Synergy

Saman Warnakulasuriya1,21Department of Oral Medicine, KingÌs College London Dental Institute at GuyÌs, KingÌs & St ThomasÌ Hospitals, WHO Collaborating Centre for Oral Cancer and Precancer, London, UK2Department of Nutrition and Dietetics, KingÌs College, London, UK, Seppo Parkkila33Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland, Toru Nagao44Department of Oral and Maxillofacial Surgery, Okazaki City Hospital, Okazaki, Japan, Victor R. Preedy1,21Department of Oral Medicine, KingÌs College London Dental Institute at GuyÌs, KingÌs & St ThomasÌ Hospitals, WHO Collaborating Centre for Oral Cancer and Precancer, London, UK2Department of Nutrition and Dietetics, KingÌs College, London, UK, Markku Pasanen5,65Department of Pharmacology, University of Oulu, Oulu, Finland6Department of Toxicology, University of Kuopio, Kuopio, Finland, Heidi Koivisto77Medical Research Unit and Department of Laboratory Medicine, Seinâjoki Central Hospital and University of Tampere, Tampere, Finland, Onni Niemelâ77Medical Research Unit and Department of Laboratory Medicine, Seinâjoki Central Hospital and University of Tampere, Tampere, Finland

Onni Niemelâ MD, Department of Laboratory Medicine, Seinâjoki Central Hospital, FIN-60220 Seinâjoki, Finland. Tel: +358 6 415 4719, Fax: +358 6 415 4924, E-mail: onni.niemela@epshp.fi
AA, acetaldehyde; MDA, malondialdehyde; HNE, 4-hydroxynonenal; CYP2E1, cytochrome P450 2E1; GSH, glutathione; SCC, squamous cell carcinoma.
J Oral Pathol Med (2007) 00: 00Ò0

Abstract
Background: Excessive alcohol consumption is a common cause for upper gastrointestinal tract cancers. However, the primary mechanisms of alcohol-induced carcinogenesis have remained poorly defined.

Method: We examined the generation and subcellular distribution of protein adducts with acetaldehyde (AA), the first metabolite of ethanol, and end products of lipid peroxidation, malondialdehyde (MDA) and 4-hydroxynonenal (HNE), from oral biopsy specimens obtained from 36 subjects (11 British, 25 Japanese) reporting alcohol misuse. All patients had been diagnosed with oral pre-cancer (leukoplakia, n = 7) or squamous cell carcinoma (SCC; n = 29). Automated immunostaining for AA, MDA and HNE adducts was performed using monospecific antibodies.

Results: Positive staining for AA, MDA and HNE adducts was observed in the dysplastic or malignant epithelial cells, HNE being relatively the most abundant adduct species. The subgroup of Japanese patients had higher levels of AA and MDA, although not HNE, than the British sample. When the material was divided to those with SCC or leukoplakia, MDA adducts but not the other antigens were more prominent in the former group. Significant correlations were found between the different adducts (AA vs. MDA, r = 0.68, P < 0.001; AA vs. HNE, r = 0.47, P < 0.01 and MDA vs. HNE, r = 0.59, P < 0.001). In addition, cytochrome P450 2E1 staining was found in these samples, correlating with both AA and MDA adducts.

Conclusion: The data indicates that AA- and lipid peroxidation-derived adducts are formed in oral tissues of alcohol misusers with oral leukoplakia and cancer. The findings also support a pathogenic role of AA and excessive oxidative stress in carcinogenesis.

Blackwell Synergy? is a Blackwell Publishing, Inc. registered trademark

This article may be viewed in its entirety by subscription or by purchase at the website.