Inhibitory effects of high temperature- and pressure-treated garlic on formation of 1,2-dimethylhydrazine-induced mucin-depleted foci and O(6)-methylguanine DNA adducts in the rat colorectum.
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.
Chihara
Takeshi
T
Fujita Memorial Nanakuri Institute, Fujita Health University, Tsu, Mie, Japan.
Shimpo
Kan
K
Kaneko
Takaaki
T
Beppu
Hidehiko
H
Tomatsu
Akiko
A
Sonoda
Shigeru
S
D019813:1,2-Dimethylhydrazine / Q000494:pharmacology; D000818:Animals; D003106:Colon / Q000187:drug effects*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D018736:DNA Adducts / Q000187:drug effects*; D005737:Garlic / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives / Q000494:pharmacology; D006358:Hot Temperature; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D055262:Mucin-2 / Q000172:deficiency*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D011230:Precancerous Conditions / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D011312:Pressure; D051381:Rats; D011916:Rats, Inbred F344; D012007:Rectum / Q000187:drug effects*
D018736:DNA Adducts; D055262:Mucin-2; D010936:Plant Extracts; D006147:Guanine; C008449:O-(6)-methylguanine; D019392:Cytochrome P-450 CYP2E1; D019813:1,2-Dimethylhydrazine