title: Impact of dioxins on antipyrine metabolism in firefighters.
abstract: Antipyrine (AP) metabolism was used to assess factors associated with the activity of hepatic oxidative enzymes in firefighters. Emphasis was placed on 3-hydroxymethylantipyrine (3HMAP), the metabolite with the greatest dependence on dioxin-inducible cytochrome P4501A2 (CYP1A2) activity. AP urinary metabolites were measured by HPLC in 38 male subjects from Eastern Siberia. Subjects were divided into three groups having similar ages and BMIs: current firefighters (n=11); former firefighters (n=17) and non-firefighters (n=10). Multiple regression models were constructed using the three major AP metabolites as a dependent variable to assess the influence of age, smoking as urinary cotinine concentration, dioxin exposure (as either WHO-TEQ or body burden), group, and CYP1A2*F (-163C>A) genotypes. Models for the proportion of dose excreted as the metabolite 3HMAP produced the best fit (adjusted R(2)=0.46, p<0.05). When the models were restricted to current firefighters, only those based on 3HMAP were statistically significant (adjusted R(2) of 0.80 (p<0.002)) due to contributions from urinary cotinine (β=0.56, p<0.01) and dioxin expressed as body burden (β=0.55, p=0.014). These results indicate that the antipyrine test can be used as metabolic probe of biological response to recent dioxin exposure provided the impact of smoking is carefully controlled.
authors.affiliation: East-Siberian Institute of Medical and Ecological Research, P.O. Box 1170, Angarsk 665827, Russia. Electronic address: yuri_chernyak@hotmail.com.
authors.forename: Yury I
authors.initials: YI
authors.lastname: Chernyak
authors.affiliation: East-Siberian Institute of Medical and Ecological Research, P.O. Box 1170, Angarsk 665827, Russia.
authors.forename: Alla P
authors.initials: AP
authors.lastname: Merinova
authors.affiliation: A.N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, 33, Leninsky prosp., Moscow 119071, Russia.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Shelepchikov
authors.affiliation: East-Siberian Institute of Medical and Ecological Research, P.O. Box 1170, Angarsk 665827, Russia.
authors.forename: Sergey I
authors.initials: SI
authors.lastname: Kolesnikov
authors.affiliation: Brooklyn College-CUNY, 2900 Bedford Avenue, Brooklyn, NY 11210-2889, USA.
authors.forename: Jean A
authors.initials: JA
authors.lastname: Grassman
mesh_terms: D000328:Adult; D000983:Antipyrine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D001822:Body Burden; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis* / Q000235:genetics; D065694:Cytochrome P-450 CYP1A2 Inducers / Q000009:adverse effects*; D004147:Dioxins / Q000009:adverse effects*; D004790:Enzyme Induction; D061388:Firefighters; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D016273:Occupational Exposure / Q000009:adverse effects*; D010641:Phenotype; D018570:Risk Assessment; D012800:Siberia; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism; D013379:Substrate Specificity; D016482:Urinalysis / Q000379:methods
chemical_list: D065694:Cytochrome P-450 CYP1A2 Inducers; D004147:Dioxins; C031820:3-hydroxymethylantipyrine; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D000983:Antipyrine
keywords: Antipyrine metabolism; Cytochrome P4501A2 (CYP1A2); Dioxin exposure; Firefighters; Urinary cotinine level