A new sensitive fluorometric assay for the metabolism of (--)-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene by human hair follicles.
A new sensitive fluorometric assay was established to measure the stereospecific formation of benzo[alpha]pyrene tetrols formed after cytochrome P450-dependent metabolism of (--)-7,8-dihydroxy-7,8- dihydrobenzo[a]pyrene by human hair follicles. This simple assay requires three human hair follicles and a low (0.5-2.0 microM) substrate concentration and has a limit of detection of approximately 0.3 fmol of tetrols. Freshly isolated human hair follicles from 20 adult volunteers (10 non-smokers and 10 smokers) were assayed. While intersubject and seasonal variations were observed, the assay was found to be reproducible for a given subject. This rapid and non-invasive assay provides a new means for metabolic phenotyping of human subjects for their capacity to metabolize (--)-7,8-dihydroxy-7,8-dihydrobenzo[alpha]pyrene to its carcinogenic form (+)anti-benzo[a]pyrene diolepoxide.
Alexandrov
K
K
Unit of Environmental Carcinogens and Host Factors, International Agency for Research on Cancer, Lyon, France.
Rojas
M
M
Goldberg
M
M
Camus
A M
AM
Bartsch
H
H
D000328:Adult; D001564:Benzo(a)pyrene / Q000378:metabolism; D001580:Benzopyrenes / Q000378:metabolism* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D005470:Fluorometry / Q000379:methods; D006197:Hair / Q000378:metabolism*; D006801:Humans; D008968:Molecular Conformation; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors
D001580:Benzopyrenes; D001564:Benzo(a)pyrene; C023393:benzo(a)pyrene 7,8-oxide