DIFFERENTIAL INDUCTION OF NAD(P)H-QUINONE OXIDOREDUCTASE BY ANTICARCINOGENIC ORGANOSULFIDES FROM GARLIC

This study was undertaken to elucidate the mechanism of organ specific ity and differential efficacy of garlic organosulfides (OSCs) [diallyl sulfide (DAS), diallyl disulfide (DPS), diallyl trisulfide (DATS), di propyl sulfide (DPS) and dipropyl disulfide (DPDS)] in preventing benz o(a)pyrene (BP)-induced tumorigenesis in mice. The results of the pres ent study reveal a good correlation between chemopreventive efficacies of garlic OSCs and their inductive effects on the expression of NAD(P )H:quinone oxidoreductase (NQO), an enzyme implicated in the detoxific ation of activated quinone metabolites of BP. Treatment of mice with D ADS and DATS, which are potent inhibitors of BP-induced forestomach tu morigenesis, resulted in a statistically significant increase (2.4- an d 1.5-fold, respectively) in forestomach NQO activity. In addition, DA DS and DATS were much more potent inducers of forestomach NQO activity than DAS, which is a weak inhibitor of BP-induced forestomach tumorig enesis than the former compounds. Propyl-group containing OSCs (DPS an d DPDS), which do not inhibit BP-induced tumorigenesis, did not affect forestomach NQO activity. Similar to forestomach, a good correlation was also observed between effects of these OSCs against BP-induced pul monary tumorigenesis and their effects on NQO expression in the lung. For example, treatment of mice with DAS, which is a potent inhibitor o f BP-induced pulmonary tumorigenesis, resulted in about 3.2-fold incre ase in pulmonary NQO activity. On the other hand, this activity was in creased by about 1.5-fold upon DATS administration, which does not inh ibit BP-induced cancer of the lung. In conclusion, our results suggest that induction of NQO may be important in anti-cancer effects of garl ic OSCs. (C) 1998 Academic Press.