Inhibitory Effects of High Temperature- and Pressure-Treated Garlic on Formation of 1,2-Dimethylhydrazine-Induced Mucin-Depleted Foci and O6-Methylguanine DNA Adducts in the Rat Colorectum

Abstract

High temperature- and pressure-treated garlic (HTPG) has been reported to have enhanced antioxidativeand cytotoxic activities. However, there have been no reports on chemopreventive effects using animal cancermodels. This study first examined the modifying effects of HTPG on 1,2-dimethylhydrazine (DMH)-inducedmucin-depleted foci (MDF) and aberrant crypt foci (ACF), preneoplastic lesions in the rat colorectum. MaleF344 rats (5 weeks old) were fed basal diet, or experimental diets containing 1% or 3% HTPG for 5 weeks. Oneweek later, all rats were injected s.c. with DMH (40 mg/kg, once weekly for 2 weeks). At 10 weeks of age, all therats were sacrificed, and the colorectum was evaluated for MDF and ACF. In rats given DMH and 3% HTPG,the numbers of MDF were decreased significantly as compared with those of rats given DMH alone (p<0.01),and the numbers of ACF showed a tendency to decrease, although not significantly. Next, the effects of HTPGon the formation of DMH-induced O6-methylguanine (O6-MeG) DNA adducts in rats were studied. Male F344rats (5 weeks old) were fed the basal diet or 10% HTPG diet for 5 weeks. All rats were injected i.p. once with 40mg/kg DMH at the end of week 5. The animals were sacrificed 6 hours after DMH injection to analyze the O6-MeG DNA adducts in the colorectal mucosa and liver. Dietary administration of HTPG significantly reducedthe adduct levels in the colorectal mucosa and liver, compared with the controls (both p<0.01). The activities ofsome detoxification enzymes in the liver of DMH-treated rats were also measured. HTPG significantly reducedthe activity of cytochrome P450 (CYP) 2E1, known to be responsible for activation of DMH in rat liver (p<0.05).In contrast, HTPG significantly enhanced the activities of phase 2 enzymes, quinone reductase (QR) andglutathione S-transferase (GST), in rat liver (both p<0.05). These results suggested that HTPG might havechemopreventive effects against colon carcinogenesis, at least in the initiation stage.