title: Cytochrome P450 1A1 MspI polymorphism and urinary 1-hydroxypyrene concentrations in coke-oven workers.
abstract: Coke-oven workers are regularly exposed to a high concentration of the benzene-soluble fraction (BSF) of total particulates, which are comprised mainly of polycyclic aromatic hydrocarbons (PAHs). A metabolite of pyrene, 1-hydroxpyrene (1-OHP), is readily measured in the urine of exposed individuals. Epidemiological studies have shown that P4501A1 (CYP1A1) genotypes are associated with PAH-related lung cancer risk. The purpose of this study was to investigate whether CYP1A1 MspI genotypes modulate the relationship of individual occupational exposure to air BSF to urinary 1-OHP concentrations among coke-oven workers. We monitored individual breathing zone air BSF over 3 consecutive days in 80 coke-oven workers in Taiwan from August 1995 to February 1996. Exposure was also dichotomized by work area (topside oven workers and sideoven workers). Preshift urine on the morning of day 1 and postshift urine on the afternoon of day 3 were measured by fluorescent spectrophotometry, and blood samples were analyzed to determine the relative distributions of CYP1A1 MspI polymorphisms. The frequency of the MspI homozygous variant genotypes of CYP1A1 was 15%. Multiple linear regression showed significant effects of individual occupational exposure to air BSF and preshift 1-OHP on postshift urinary 1-OHP concentrations (P = 0.002 and P < 0.001, respectively). After adjusting for preshift 1-OHP concentrations and air BSF, subjects with the homozygous variant genotype have a 2-fold higher postshift 1-OHP levels than the combined wild-type and heterozygous (P = 0.04). In addition, a positive trend was found in postshift 1-OHP and across-shift change of 1-OHP (postshift 1-OHP - preshift 1-OHP) in decreasing order, as follows: topside oven workers with the homozygous variant trait, topside oven workers with the heterozygous variant trait, sideoven workers with the homozygous variant trait, and sideoven workers with the heterozygous trait (P < 0.001). We conclude that CYP1A1 MspI variant genotype can modify the metabolism of PAHs in coke-oven workers.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Wu
authors.forename: S L
authors.initials: SL
authors.lastname: Huang
authors.forename: C K
authors.initials: CK
authors.lastname: Ho
authors.forename: Y F
authors.initials: YF
authors.lastname: Yeh
authors.forename: D C
authors.initials: DC
authors.lastname: Christiani
mesh_terms: D000328:Adult; D000368:Aged; D003077:Coke / Q000009:adverse effects*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism; D019003:Deoxyribonuclease HpaII / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D016273:Occupational Exposure; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects / Q000378:metabolism; D011110:Polymorphism, Genetic; D011721:Pyrenes / Q000378:metabolism*; D012044:Regression Analysis; D012907:Smoking / Q000009:adverse effects
chemical_list: D003077:Coke; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; D019363:Cytochrome P-450 CYP1A1; D019003:Deoxyribonuclease HpaII; C033146:1-hydroxypyrene