title: Human peripheral lymphocytes as indicators of microsomal epoxide hydrolase activity in liver and lung.
abstract: In this study, we have applied an improved assay for the determination of microsomal epoxide hydrolase activity to assess enzymatic levels in human lung, liver, and blood lymphocytes. The assay is fluorescence-based and monitors the epoxide hydrolase-mediated conversion of (+/-)-benzo[a]pyrene-4,5-epoxide to (+/-)-trans-benzo[a]pyrene-4,5-dihydrodiol, using a high pressure liquid chromatography separation system. Approximately a 40-fold range in microsomal epoxide hydrolase activities was detected in blood lymphocytes collected from 70 individual donors. In 38 individuals who were sampled twice after a 3-month interval, the repeatability of an individual's lymphocyte epoxide hydrolase activity was highly correlated (r = 0.80, p < 0.02). In addition, within the same individual there appeared to be a strong correlation between lymphocyte and liver epoxide hydrolase activity (r = 0.92, p = 0.02), and some correlation between liver and lung activity (r = 0.58, p = 0.05). Activities were assessed in lymphocytes from a styrene-exposed worker population but no significant associations between blood concentrations of styrene and epoxide hydrolase activity levels were observed. Neither were any correlations detected in these workers between epoxide hydrolase activities and age, years on the job, alcohol consumption, sex, or smoking status. The results of our study suggest that blood lymphocytes are a useful sentinel cell for epoxide hydrolase activity determinations in individuals, as these measures are relatively stable over time and appear to reflect activity levels in other target organs.
authors.affiliation: Department of Environmental Health, University of Washington, School of Public Health and Community Medicine, Seattle 98195.
authors.forename: C J
authors.initials: CJ
authors.lastname: Omiecinski
authors.forename: L
authors.initials: L
authors.lastname: Aicher
authors.forename: R
authors.initials: R
authors.lastname: Holubkov
authors.forename: H
authors.initials: H
authors.lastname: Checkoway
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D004851:Epoxide Hydrolases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008168:Lung / Q000201:enzymology*; D008214:Lymphocytes / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology*; D008875:Middle Aged; D016273:Occupational Exposure; D013050:Spectrometry, Fluorescence; D020058:Styrene; D013343:Styrenes / Q000097:blood / Q000633:toxicity
chemical_list: D013343:Styrenes; D020058:Styrene; D004851:Epoxide Hydrolases