Combinatorial antigenotoxic and anticarcinogenic effects of tomato and garlic through modulation of xenobiotic-metabolizing enzymes during hamster buccal pouch carcinogenesis

Abstract

Objective Combination chemoprevention by dietary agents is a promising approach toward cancer control. Many dietary agents are known to prevent experimental mutagenesis and carcinogenesis by modulating xenobiotic-metabolizing enzymes. The present study evaluated the combinatorial chemopreventive effects of tomato and garlic on hamster buccal pouch carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA). Methods Hamsters were assigned to one of four groups. The right buccal pouches of animals in group 1 were painted with 0.5% DMBA three times a week. The right buccal pouches of animals in group 2 were painted with DMBA and received intragastric administration of a combined dose of tomato and garlic on days alternate to DMBA application. Animals in group 3 were given chemopreventive agents alone. Animals in group 4 served as controls. Levels of phase I and II enzymes and the frequency of bone marrow micronuclei were used as biomarkers of chemoprevention. Results All the hamsters painted with DMBA alone developed buccal pouch carcinomas that exhibited increased activities of xenobiotic-metabolizing enzymes associated with increased frequencies of bone marrow micronuclei. In the liver, an increase in phase I enzymes was accompanied by compromised phase II detoxification activities. Combined administration of tomato and garlic effectively suppressed the incidence and mean tumor burden of hamster buccal pouch carcinomas. In addition, tomato and garlic combination significantly decreased phase I enzymes and increased phase II enzyme activities in the pouch and liver with a decreased incidence of bone marrow micronuclei. Conclusion From these results, we suggest that modulation of xenobiotic-metabolizing enzymes exerted by tomato and garlic combination plays a key role in mitigating the mutagenic and carcinogenic effects of DMBA.