CYP2A6/2A7 and CYP2E1 expression in human oesophageal mucosa: Regional and inter-individual variation in expression and relevance to nitrosamine metabolism

Godoy, Wagner, Albano, Rodolpho M., Moraes, Emanuela G., Pinho, Paulo R. Alves, Nunes, Rodolfo A., Saito, Eduardo H., Higa, Cláudio, Filho, Ivan M., Kruel, Cleber D. Pinto, Schirmer, Carlos C., Gurski, Richard, Lang, Matti A. and Pinto, Luis F. Ribeiro (2002) CYP2A6/2A7 and CYP2E1 expression in human oesophageal mucosa: Regional and inter-individual variation in expression and relevance to nitrosamine metabolism. Carcinogenesis, 23 4: 611-616.


Author Godoy, Wagner
Albano, Rodolpho M.
Moraes, Emanuela G.
Pinho, Paulo R. Alves
Nunes, Rodolfo A.
Saito, Eduardo H.
Higa, Cláudio
Filho, Ivan M.
Kruel, Cleber D. Pinto
Schirmer, Carlos C.
Gurski, Richard
Lang, Matti A.
Pinto, Luis F. Ribeiro
Title CYP2A6/2A7 and CYP2E1 expression in human oesophageal mucosa: Regional and inter-individual variation in expression and relevance to nitrosamine metabolism
Journal name Carcinogenesis   Check publisher's open access policy
ISSN 0143-3334
1460-2180
Publication date 2002-04
Sub-type Article (original research)
DOI 10.1093/carcin/23.4.611
Volume 23
Issue 4
Start page 611
End page 616
Total pages 6
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract Oesophageal cancer is one of the most common and lethal malignancies in the world. Despite many efforts, treatment is still ineffective for most cases; thus, the development of preventive strategies is crucial for decreasing the burden presented by this disease. Environmental factors, particularly nitrosamines, are thought to be involved in the genesis of oesophageal tumours, and knowledge about the expression of enzymes capable of activating pre-carcinogens in human oesophagus is very important for the development of preventive measures. We analysed the expression of CYP1A1, CYP1A2, CYP2A6/2A7, CYP2E1 and CYP3A4 mRNA in oesophageal mucosa of 50 patients by semi-quantitative RT-PCR. In five patients, who suffered from squamous cell carcinoma, we measured Nnitrosodimethylamine and N-nitrosodiethylamine metabolism in normal and tumorous tissue. CYP2A6/2A7 mRNA was expressed in 61% and CYP2E1 mRNA in 96% of the patients, but in the latter a lower degree of inter-individual variation was observed. These enzymes were expressed either in the distal or middle portions of the oesophagus of 90% of the patients. CYP1A1, CYP1A2 and CYP3A4 mRNA expression was not detected in any portion of the oesophagus. Oesophageal microsomes activated N-nitrosodimethylamine with a low degree of inter-individual variation and microsomes prepared from the tumour of a patient who strongly expressed CYP2A6/2A7 mRNA activated N-nitrosodiethylamine. We conclude that the human oesophagus expresses CYP2A6/2A7 and CYP2E1 and can activate nitrosamines. Notably, the expression of these enzymes is preferentially localized to the most common sites where tumours arise.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
 
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