MECHANISM OF DIFFERENTIAL EFFICACY OF GARLIC ORGANOSULFIDES IN PREVENTING BENZO(A)PYRENE-INDUCED CANCER IN MICE

The mechanism of differential efficacies of diallyl sulfide (DAS), dia llyl disulfide (DADS), diallyl trisulfide (DATS), dipropyl sulfide (DP S) and dipropyl disulfide (DPDS) in preventing benzo(a)pyrene (BP)-ind uced cancer in mice has been investigated by determining their effects on the enzymes of BP activation/inactivation pathways. With the excep tion of DATS, treatment of mice with other organosulfides (OSCs) cause d a small but significant increase (37-44%) in hepatic ethoxyresorufin O-deethylase (EROD) activity. However, the forestomach EROD activity did not differ significantly between control and treated groups. Only DAS treatment caused a modest but statistically significant reduction (about 25%) in pulmonary EROD activity. These results suggest that whi le reduction of EROD activity may, at least in part, contribute to the DAS-mediated inhibition of BP-induced lung cancer, anticarcinogenic e ffects of OSCs against BP-induced forestomach carcinogenesis seems to be independent of this mechanism. Treatment of mice with DAS, DADS and DATS resulted in a significant increase, as compared with control, in both hepatic (3.0-, 3.2- and 4.4-fold, respectively) and forestomach (1.5-, 2.7- and 2.7-fold, respectively) glutathione transferase (GST) activity toward anti-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-oxy-7,8 ,9,10-tetrahydrobenzo(a)pyrene (anti-BPDE), which is the ultimate carc inogen of BP. The pulmonary GST activity was not increased by any of t he OSCs. Even though epoxide hydrolase (EH) activity was differentiall y altered by these OSCs, a correlation between chemopreventive efficac y of OSCs and their effects on EH activity was not apparent. The resul ts of the present study suggest that differences in the ability of OSC s to modulate GST activity toward anti-BPDE may, at least in part, acc ount for their differential chemopreventive efficacy against BP-induce d cancer in mice. (C) 1997 Elsevier Science Ireland Ltd.