Combination
chemoprevention by diet-derived agents is a promising strategy for protection against
gastric cancer. We therefore evaluated the combined chemopreventive effect of
S-allylcysteine (SAC), an organosulfur constituent of garlic, and
lycopene, a major
carotenoid present in tomatoes, against
N-methyl-N'-nitro-N-nitrosoguanidine (
MNNG) and saturated
sodium chloride (S-NaCl)-induced gastric
carcinogenesis in Wistar rats. The animals were divided into eight groups of six animals each. Rats in group 1 were given
MNNG by intragastric intubation on days 0 and 14 as well as S-NaCl every 3 days during weeks 0-3. Animals in groups 2-4, administered
MNNG and S-NaCl as in group 1, received in addition SAC and
lycopene alone and in combination, respectively, three times per week starting on the day following the first exposure to
MNNG. Groups 5-7 were given the chemopreventive agents alone, whereas group 8 served as controls. The animals were sacrificed after an experimental period of 21 weeks. Measurement of lipid peroxidation and
antioxidants of the
glutathione redox cycle in the stomach, liver, and erythrocytes was used to monitor the chemopreventive potential of SAC and
lycopene. In the
tumor tissue, diminished lipid peroxidation was accompanied by an increase in
reduced glutathione (GSH) and GSH-dependent
enzymes, whereas in the liver and erythrocytes, enhanced lipid peroxidation was associated with
antioxidant depletion. Although SAC and
lycopene alone significantly suppressed the development of
gastric cancer, administration of SAC and
lycopene in combination was more effective in inhibiting
MNNG-induced stomach
tumors and modulating the redox status in the
tumor and host tissues. The results of the present study validate the hypothesis that diet-derived chemopreventive agents such as SAC and
lycopene in combination may interact synergistically with high efficacy and lessened toxicity against
gastric cancer.