CYP2A6/2A7 and CYP2E1 expression in human oesophageal mucosa: regional and inter-individual variation in expression and relevance to nitrosamine metabolism.
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.
Godoy
Wagner
W
Departamento de Bioquímica, IBRAG, Universidade do Estado do Rio de Janeiro, RJ, Brazil.
Albano
Rodolpho M
RM
Moraes
Emanuela G
EG
Pinho
Paulo R Alves
PR
Nunes
Rodolfo A
RA
Saito
Eduardo H
EH
Higa
Cláudio
C
Filho
Ivan M
IM
Kruel
Cleber D Pinto
CD
Schirmer
Carlos C
CC
Gurski
Richard
R
Lang
Matti A
MA
Pinto
Luis F Ribeiro
LF
D000477:Alkylating Agents / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases; D002294:Carcinoma, Squamous Cell / Q000201:enzymology; D065637:Cytochrome P-450 CYP2A6; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D000072467:Cytochrome P450 Family 2; D004052:Diethylnitrosamine / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000378:metabolism; D004947:Esophagus / Q000201:enzymology*; D006801:Humans; D008861:Microsomes / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D009061:Mouth Mucosa / Q000201:enzymology*; D009062:Mouth Neoplasms / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000477:Alkylating Agents; D012333:RNA, Messenger; D004052:Diethylnitrosamine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; C423964:CYP2A7 protein, human; D065637:Cytochrome P-450 CYP2A6; D000072467:Cytochrome P450 Family 2; D004128:Dimethylnitrosamine