The addition of lipid hydroperoxides greatly accelerates the rate of oxidative catabolism of all-Irans-retinoic acid (RA) in human cell micro somes; hydroperoxy metabolites of the arachidonate cascade are partic

The addition of lipid hydroperoxides greatly accelerates the rate of oxidative catabolism of all-Irans-retinoic acid (RA) in human cell micro somes; hydroperoxy metabolites of the arachidonate cascade are partic ularly active in the microsomabsystem. We have measured the plasma content oflipid peroxides in cancer patients during the course of therapy with RA, seeking to assess whether a correlation exists between the rate of oxidative catabolism of exogenousbyadministered RA and whole body lipid peroxide levels. The assay used for plasma lipid peroxides is the capacity to react with thiobarbituric acid under specified conditions; the result is expressed as TBARS (thiobarbituric acid reactive substances). RA administration produced its own accelerated clearance RA within 72 h. Patients were considered to have “normal― or “rapid― baseline catab olism of HA if their Day 1 area under BA concentration over time curve was greater or less than 300 ng'h/ml, respectively. The mean plasma ThARS levels were: 12 normal volunteers = 0.14 @M; 19 “normal― RA catabolizers = 0.25 sM; and 14 “rapid― catabobizers = 0.82 saM.P = 0.008 (rapid catabolizers versus normal volunteers) and 0.05 (rapid catabolizers versus normal catabolizers). Repeat ThARS determinations were made during the course of therapy in 17 patients, all of whom converted to “rapid― RA catabolism on therapy. An increase in plasma TRARS bevels 20% ofbasellne was observed in 5 of5 prostate cancer patients and 8 of 12 lung cancer patients treated with continuous RA therapy for 2 and 4 weeks, respectively. These observations support the hypothesis that high bevelsof lipid peroxides and rapid oxidative catabolism of PA are posi lively correlated.