High temperature- and pressure-treated garlic (HTPG) has been reported to have enhanced antioxidative and cytotoxic activities. However, there have been no reports on chemopreventive effects using animal
cancer models. This study first examined the modifying effects of HTPG on
1,2-dimethylhydrazine (
DMH)-induced
mucin-depleted foci (
MDF) and
aberrant crypt foci (ACF), preneoplastic lesions in the rat colorectum. Male F344 rats (5 weeks old) were fed basal diet, or experimental diets containing 1% or 3% HTPG for 5 weeks. One week later, all rats were injected s.c.with
DMH (40 mg/kg, once weekly for 2 weeks).
At 10 weeks of age, all the rats 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 HTPG on the formation of
DMH-induced
O6-methylguanine (O6-MeG)
DNA adducts in rats were studied. Male F344 rats (5 weeks old) were fed the basal diet or 10% HTPG diet for 5 weeks. All rats were injected i.p. once with 40 mg/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 reduced the adduct levels in the colorectal mucosa and liver, compared with the controls (both p< 0.01). The activities of some detoxification
enzymes in the liver of
DMH-treated rats were also measured. HTPG significantly reduced the 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) and
glutathione S-transferase (GST), in rat liver (both p< 0.05). These results suggested that HTPG might have chemopreventive effects against colon
carcinogenesis, at least in the initiation stage.