Profile of urinary phenanthrene metabolites in smokers and non-smokers

Citation
J. Jacob et al., Profile of urinary phenanthrene metabolites in smokers and non-smokers, BIOMARKERS, 4(5), 1999, pp. 319-327
Citations number
37
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOMARKERS
ISSN journal
1354750X → ACNP
Volume
4
Issue
5
Year of publication
1999
Pages
319 - 327
Database
ISI
SICI code
1354-750X(199909/10)4:5<319:POUPMI>2.0.ZU;2-U
Abstract
Phenanthrene metabolites (phenols and dihydrodiols) and l-hydroxypyrene exc reted in the 24-h urine of smokers, non-smokers and lung cancer patients, w ho after heavy smoking became light smokers, were determined and compared. In contrast to 1-hydroxypyrene, no significant differences of the absolute amounts of phenanthrene metabolites were found between smokers and non-smok ers. A ratio phenanthrene metabolites/1-hydroxypyrene of 10.4 was observed for non-smokers and 9.9 for lung cancer patients, but 4.2 for smokers. Sign ificantly different ratios for the regiospecific oxidation of phenanthrene were found for smokers when compared with non-smokers (1,2-oxidation vs 3,4 -oxidation was 1.45 in the case of smokers, but 2.34 in the case of non-smo kers) indicating a cigarette smoke- but not PAM-caused induction of CYP 1A2 in smokers. As a consequence of the degree of PAH exposure the ratio dihyd rodiols/phenols depends on the total amount of metabolites excreted. Phenol s predominate, equally in smokers and non-smokers after low exposure, while dihydrodiols become more prominent in highly exposed persons (coke plant w orkers). Both (i) the regiospecific oxidation of PAH and (ii) the ratio of dihydrodiol vs phenol formation may be recognized from the urinary phenanth rene metabolite profile. This pattern mirrors the enzymatic status (balance of the CYP isoforms and epoxide hydrolase) in individuals. Accordingly, mo re detailed information may be obtained from the urinary metabolite pattern than from 1-hydroxypyrene, commonly used in PAH biomonitoring.