THE INFLUENCE OF CYTOCHROME-P450 ENZYME-ACTIVITY ON THE COMPOSITION AND QUANTITY OF VOLATILE ORGANICS IN EXPIRED BREATH

We have previously described a method to capture, identify and quantif y volatile components in expired breath. The purpose of this research is to provide a non-invasive means to measure biomarkers of metabolism in vivo. In the present studies, the effect of 1-aminobenzotriazole ( ABT), an inhibitor of diverse cytochrome P450 (P450) enzymes, on the c omposition of volatile organic chemicals (VOCs) expired in the breath of male F-344 rats was determined in parallel with the catalytic activ ities and total content of hepatic P450. Intraperitoneal administratio n of ABT (100 mg kg(-1)) to rats resulted in markedly diminished hepat ic microsomal P450 content and activities. The extent of inhibition wa s near maximal at 4 h, at which time approximately 50% of the total P4 50 content, about 65% of the CYP1A2 activity, 55% of the CYP2E1 activi ty and about 80% of CYP2B activity were lost. inhibition was maintaine d to 48 h post-dosing, but P450 content and activities had largely bee n restored by day 7. Concomitant with the inhibition of P450 were corr esponding increases (up to several hundred-fold) in the molar amount o f volatiles appearing in the breath of ABT-treated animals, and the re bound of P450 levels was attended by corresponding decreases in the ap pearance of breath volatiles. These studies indicate that P450 plays a major role in the metabolism of VOCs appearing in breath, and that th ese chemicals can serve as markers on P450 activity in vivo.