| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2598471 | Toxicology Letters | 2016 | 7 Pages |
•Firefighter exposure to dioxins was assessed using a metabolic test.•Current firefighters excreted metabolites consistent with CYP1A2 induction.•Recent, but not former exposure, alters the metabolism of firefighters.
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 R2 = 0.46, p <0.05). When the models were restricted to current firefighters, only those based on 3HMAP were statistically significant (adjusted R2 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.
