Cytochrome p450 and glutathione transferase expression in squamous cell cancer.
OBJECTIVE
The cytochrome P-450 (CYP) and glutathione S-transferase (GST) enzyme systems modulate the carcinogenic effects of tobacco. Therefore, the expression of these enzymes may be in part responsible for the observed interindividual and inter-racial differences in the risk of development of squamous cell carcinoma of the head and neck (SCCHN). The first aim of this study was to evaluate the feasibility of measuring the expression of the CYP and GST in target tissue from the head and neck. The second aim was to compare the expression of CYPs 1A1, 2E1, and 3A4 in squamous epithelium from African-American and Caucasian pediatric patients. The third aim was to compare the expression of CYPs 1A1, 2E1, 3A4, and GST-pi on the p16 expression in patients with SCCHN.


METHODS
The expression of CYP 1A1, 2E1, 3A4, GST-pi, and p16 was quantified by immunoblotting. Expression of CYPs 1A1, 2E1, and 3A4 was quantified in tissue from 160 pediatric patients undergoing tonsillectomy. Expression of CYPs 1A1, 2E1, 3A4, GST-pi, and p16 was determined in 46 resected SCCHN patients.


RESULTS
Large interindividual variability in the expression of these enzymes was observed in the pediatric and adult populations. No significant difference was observed in CYP 1A1, 2E1, and 3A4 expression of Caucasian and African-American patients. There was no correlation between p16 and enzyme expression in patients with SCCHN.


CONCLUSIONS
Evaluation of CYP expression in the target tissue of interest is feasible. The clinical significance of CYPs and GST-pi alterations in the risk of developing SCCHN will need to be investigated in larger trials.
Ali
Shadan
S
Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.
El-Rayes
Basil F
BF
Heilbrun
Lance K
LK
Sarkar
Fazlul H
FH
Ensley
John F
JF
Kucuk
Omar
O
Philip
Philip A
PA
D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D005260:Female; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000096:biosynthesis*; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D009369:Neoplasms / Q000201:enzymology*; D010100:Oxygen / Q000378:metabolism
D019941:Cyclin-Dependent Kinase Inhibitor p16; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; C104464:CYP3A protein, human; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D010100:Oxygen