7-Ethoxyresorufin-O-deethylase activity in human hair roots: a potential marker for toxifying species of cytochrome P-450 isozymes.
Assay systems for the evaluation of carcinogen interaction with human tissues are essential for assessing cancer risk. Human hair roots (HHR) are a readily obtainable epithelial tissue source that have been employed for investigating inherited enzyme activities. In this study HHR were found to possess cytochrome P-450-dependent 7-ethoxyresorufin-O-deethylase (ERD) activity which measures cytochrome P-450 isoenzymes that are highly specific (in the order of greater than 95%) markers for the metabolic activation of many environmental carcinogenic substances such as the polycyclic aromatic hydrocarbons (PAHs). Topical application of PAHs (in liquor carbonis detergens) to the scalp of human volunteers was found to enhance the activity of this enzyme in freshly plucked hair roots. Oral and topical administration of ketoconazole to the same subjects resulted in an appreciable (up to 73%) inhibition of detectable enzyme activity. Our data suggest that measurement of ERD in HHR may be a useful marker for the study of toxifying species of cytochrome P-450 isozymes in human populations.
Merk
H F
HF
Department of Dermatology, University of Cologne, Koeln, West Germany.
Mukhtar
H
H
Schutte
B
B
Kaufmann
I
I
Das
M
M
Bickers
D R
DR
D002273:Carcinogens / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006197:Hair / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D010088:Oxidoreductases / Q000378:metabolism*; D012535:Scalp
D002273:Carcinogens; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1