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

Takeshi Chihara, Kan Shimpo, Takaaki Kaneko, Hidehiko Beppu, Akiko Tomatsu, Shigeru Sonoda

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)827-832
Number of pages6
JournalAsian Pacific Journal of Cancer Prevention
Volume10
Issue number5
Publication statusPublished - 01-01-2009

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1,2-Dimethylhydrazine
Garlic
Dimethylhydrazines
DNA Adducts
Mucins
Pressure
Temperature
Aberrant Crypt Foci
Liver
Diet
Inbred F344 Rats
Mucous Membrane
O-(6)-methylguanine
NAD(P)H Dehydrogenase (Quinone)
Cytochrome P-450 CYP2E1
Enzymes
Glutathione Transferase
Colon
Carcinogenesis
Animal Models

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology
  • Public Health, Environmental and Occupational Health
  • Cancer Research

Cite this

@article{7f83e36f71974aba9f005eb9ccc3537c,
title = "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 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.",
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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. / Chihara, Takeshi; Shimpo, Kan; Kaneko, Takaaki; Beppu, Hidehiko; Tomatsu, Akiko; Sonoda, Shigeru.

In: Asian Pacific Journal of Cancer Prevention, Vol. 10, No. 5, 01.01.2009, p. 827-832.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Chihara, Takeshi

AU - Shimpo, Kan

AU - Kaneko, Takaaki

AU - Beppu, Hidehiko

AU - Tomatsu, Akiko

AU - Sonoda, Shigeru

PY - 2009/1/1

Y1 - 2009/1/1

N2 - 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.

AB - 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.

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