Relationship between polychlorinated biphenyl 126 treatment and cytochrome p4501a activity in chickens, as measured by in vivo caffeine and ex vivo ethoxyresorufin metabolism

Abstract

Cytochrome P4501A (CYP1A) activity is often used as a biomarker of exposure of wildlife to polyhalogenated diaromatic hydrocarbons (PHDHs) and is usually measured ex vivo in liver tissue. A caffeine breath test with radiolabelled substrate (14C-CBT) has been developed to measure in vivo avian CYP1A activity. Research goals were to develop stable isotope methods (13C-CBT), determine dose-response relationships between caffeine N-demethylation (CNDM) and PHDH exposure, and assess the relative utility of the CBT and ex vivo ethoxyresorufin-O-deethylase (EROD) assay. The 13C-CBT methods were developed with 20 chickens (Gallus domesticus). Chickens received three intraperitoneal injections of 0, 1, 5, or 50 μg 3,3′,4,4′,5-pentachloro-biphenyl (PCB 126)/kg body weight, and CNDM was quantified by measurement of 13CO2/12CO2 in expired breath. The 13C-CBT was not as sensitive or specific as the EROD assay as an indicator of PHDH exposure and effect in birds. Constitutive CNDM of great interindividual variability was observed, and the magnitude of induction was greater for EROD activity than for CNDM (approximately 1,000- and 2-fold, respectively). Variability associated with baseline 13CO2/12CO2 ratios in expired breath reduced the sensitivity of the 13C-CBT method.