BASIS FOR THE ANTITUMOR AND CHEMOPREVENTIVE ACTIVITIES OF GLUCARATE AND THE GLUCARATE-RETINOID COMBINATION

The biochemical basis for the cancer chemopreventive and anti-cancer a ctivities of glucarate, retinoids (13-cis-retinoic acid, hydroxyphenyl retinamide) and their synergistic combination, has been evaluated. Ne ither alone nor in combination did these agents affect the level in th e rat, of enzymes which are (a) known to correlate with reduced risk o f carcinogenesis (detoxification enzyme, catalase, glutathione reducta se) nor (b) enzymes which correlate with increased risk of carcinogene sis (beta-glucuronidase, xanthine oxidase, glucose-6-phosphate dehydro genase). Retinoids, but neither glucarate nor its lactone inhibited fr ee radical-induced lipid peroxidation. Both agents alone and synergist ically in combination, raise cellular cAMP levels, repress protein kin ase C and more generally inhibited DNA synthesis.