Protective effects of trifluralin on benzo(a)pyrene-induced tumors in A/J mice

Trifluralin, a widely used herbicide, added to the diet before the p.o. administration of benzo(a)pyrene (BP) and fed continuously, significantly inhibited the induction of lung and forestomach tumors in female A/J mice. Dietary intake of trifluralin before the administration of BP resulted in a significant increase in glutathione in lung and forestomach but not in liver and glandular stomach. Trifluralin treatment also inhibited the binding of [3H]BP to liver and lung DNA, as well as to protein in the liver. Under these conditions, the protection against BP-induced lung tumors and perhaps forestomach tumors may be due to an elevation of tissue glutathione, resulting in a decreased binding of reactive metabolites of BP to macromolecules at these sites. The results indicate that trifluralin has a "blocking" effect in its inhibition of BP-induced tumors. Our studies show that trifluralin also inhibits chemical carcinogenesis in lung and forestomach when started in the diet 1 day after the administration of BP and fed continuously thereafter. In the case of lung, although maximum inhibition of tumors occurred when trifluralin was started 1 day after BP, there was significant protection at all time intervals (0 to 7 days) against lung tumors. The finding that trifluralin protects against BP tumorigenesis when started in the diet after the administration of the carcinogen clearly demonstrates that trifluralin also has a "suppressive" effect against BP-induced tumors.