PARAMAGNETIC-RESONANCE IN DETECTING CARCINOGENIC RISK FROM CYTOCHROME-P450 OVEREXPRESSION

Background: Despite the increasing interest in the role of oxygen radi cals on human degenerative disorders including cancer, oxidative stres s status is not yet measurable in vivo, largely precluding clinical ap plication. Limited semi-quantitative assays of damage to broad classes of biomolecules such as lipids, proteins, and DNA are currently avail able. The detection of radicals in humans by a whole-body electron par amagnetic resonance (EPR) technique has not yet been developed, althou gh this possibility has long fascinated free radical investigators. Me thods: While the EPR spin trapping procedure can be used to detect car bon centered or hydroxyl radicals in human tissues, the most common sp in traps are much less useful for capturing the superoxide anion (O-2( .-)), To overcome these limitations, we propose a whole-body-harvest a pproach that utilizes a highly lipophilic spin scavenger that when inj ected in the animal is capable of trapping the O-2(.-) generated in vi vo throughout the body with formation of a stable nitroxide measurable by EPR in the urine. A process known to generate the O-2(.-) is the i nduction of certain cytochrome P450 (CYP) isozymes by drugs or environ mental pollutants. Results: We report: 1) a correlation between the in duction of each CYP gene family and the O-2(.-) yield; 2) support to a n observation reported previously that the tumor promoting ability of CYP inducers is mainly mediated by the O-2(.-); and 3) the description of a method for nitroxide mediated O-2(.-) detection in vivo. Conclus ion: These findings could open the way for using electron spin resonan ce in diagnostic practice.