Experimental colon cancer

LaMont, J. Thomas; O'Gorman, T

doi:10.1016/0016-5085(78)90093-8

Cited by 149 publications

(29 citation statements)

References 90 publications

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“…Dimethylhydrazine is a widely used and highly specific carcinogen for the induction of CRC in rats, providing a model that is known closely to parallel the presentation and gross and microscopic pathology of human CRC . Rahman et al .…”

Section: Discussionmentioning

confidence: 99%

A predictive biomarker for altered 5‐fluorouracil pharmacokinetics following repeated administration in a rat model of colorectal cancer

Kobuchi

Kuwano

Imoto

et al. 2013

Biopharm & Drug Disp

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The relationship between the plasma ratio of dihydrouracil/uracil (UH2/Ura) and hepatic dihydropyrimidine dehydrogenase (DPD) activity after repeated 5-fluorouracil (5-FU) treatment in rats with colorectal cancer (CRC) was investigated. Repeated intravenous 5-FU bolus injections resulted in a significant decrease in the total clearance (CLtot ) and an increased area under the curve (AUC0-∞ ) in CRC rats. Furthermore, the hepatic DPD levels and the plasma ratio of UH2/Ura decreased significantly and lost their circadian rhythms in CRC rats treated repeatedly with 5-FU, although significant circadian variation in the two parameters was observed in the control CRC rats. Moreover, a significant correlation was found between the plasma ratio of UH2/Ura and hepatic DPD activity in CRC rats untreated and treated with single or repeated 5-FU administration (r(2) = 0.865, p < 0.01). The ratio of UH2/Ura in plasma could be a predictive biomarker of the suppression of hepatic DPD levels during repeated 5-FU-based treatment. Furthermore, by plotting the observed pharmacokinetic parameters of 5-FU against hepatic DPD activity levels predicted by the ratio of UH2/Ura in plasma, AUC0-∞ , CLtot and half-life (t1/2 ) were closely linked to predicted hepatic DPD activity levels. These observations suggest that the factor that significantly influences the AUC0-∞ , CLtot and t1/2 of 5-FU after single or repeated administration of 5-FU is the hepatic DPD activity and it could be assessed by the ratio of UH2/Ura in plasma.

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Section: Discussionmentioning

confidence: 99%

A predictive biomarker for altered 5‐fluorouracil pharmacokinetics following repeated administration in a rat model of colorectal cancer

Kobuchi

Kuwano

Imoto

et al. 2013

Biopharm & Drug Disp

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“…In our previous studies, we have shown in experimental model that NSAIDs can alter the nutrient transport (Kaushal and Sanyal, 2006), affect membrane fluidity , affect the activities of disaccharide hydrolases , recover the antioxidant enzymes (Nair et al, 2006), and remarkably reduce the precancerous lesions in rat colon induced by 1,2-dimethylhydrazine (DMH) (Kanwar et al, 2007). DMH is a colonic procarcinogen that requires metabolic activation within the host to become active (La Mont and O'Gorman, 1978), and DMH-induced tumors closely parallel human cancers in clinical and pathologic features (Luigeman and Garner, 1972).…”

Section: Introductionmentioning

confidence: 99%

Chemopreventive Effects of Nonsteroidal Anti-Inflammatory Drugs in the Membrane Lipid Composition and Fluidity Parameters of the 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis in Rats

Kanwar

Vaiphei

Nehru

et al. 2007

Drug and Chemical Toxicology

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Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, celecoxib, and etoricoxib are reported to act as chemopreventive agents in experimental colon cancer induced by 1,2-dimethylhydrazine (DMH) as they are known cyclooxygenase (COX) enzyme inhibitors. To determine whether NSAIDs can also effectively modulate the membrane lipid compositions and the fluidity parameters of colonic brush border membrane, rats were injected subcutaneously (s.c.) with DMH 30 mg/kg body weight per week for 6 weeks. The animals were simultaneously treated with NSAIDs orally at the dose of aspirin, 60 mg/kg body weight; celecoxib, 6 mg/kg body weight; and etoricoxib, 0.6 mg/kg body weight. The animals were sacrificed after 6 weeks of treatments. Brush border membrane was isolated from proximal and distal portions of the colon. Membrane lipids were extracted and analyzed while the fluidity parameters were assessed by steady-state fluorescence polarization technique using the membrane extrinsic fluorophore 1,6-diphenyl-1,3,5-hexatriene (DPH). The translational diffusion was measured by using the excimer formation of pyrene incorporated in the membrane. Colonic mucosal changes in DMH alone and DMH+NSAID treated animals were assessed histologically. The results demonstrate that (a) there is a distinct occurrence of premalignant alterations in DMH-induced colon in the form of multiple plaque lesions (MPLs), which were greatly reduced by the NSAIDs used, (b) the membrane lipid changes in DMH-induced colon were completely restored back, (c) the alterations in membrane fluorescence polarization and the fluidity parameters are partially recovered, particularly with etoricoxib, and (d) the pyrene excimer formation process was completely restored. It may be concluded that the NSAIDs, particularly the coxib group of the drugs (COX-2 selective), are effective in chemoprevention in the DMH-induced colon carcinogenesis and membrane alterations.

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“…In the present study, rats received GSH in the drinking water daily for 30 weeks. The GSH concentration in the gut may not be sufficient at any time point to protect the colon mucosa from the damaging alkylating activity of the methyl carbonium ion, a metabolite of DMH metabolism (19,20). GSH dissolved in the drinking water was not observed to enhance the colon mucosal GSH level.…”

Section: Discussionmentioning

confidence: 96%

Cruciferous vegetables and glutathione: Their effects on colon mucosal glutathione level and colon tumor development in rats induced by DMH

1995

Nutrition and Cancer

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The effect of a diet containing 10-40% lyophilized cabbage or broccoli as cruciferous vegetable or 10-40% lyophilized potato as noncruciferous vegetable fed for 14 days on the colon mucosal glutathione (GSH) level was studied in male rats. The GSH levels of the duodenum mucosa and the liver were also measured. Cabbage and broccoli enhanced the colon and duodenum mucosal GSH levels in a dose-related manner; potato had no effect. All three vegetables had no effect on the liver GSH level. The effect of GSH on colon tumorigenesis induced by 1,2-dimethylhydrazine (DMH) was also examined in rats. Male Sprague-Dawley rats were injected with DMH (20 mg/kg body wt) weekly for 20 weeks. DMH lowered the colon mucosal GSH level. GSH (100 mg/day/rat) dissolved in the drinking water and given to rats during and after DMH injections had little or no effect on tumor incidence and total number of colon tumors. Tumors were larger in rats that received GSH than in those that received water. This study shows that the colon mucosal GSH level can be enhanced by feeding rats a diet high in cabbage or broccoli and that GSH added to the drinking water did not affect DMH-induced colon tumorigenesis under the experimental conditions used.

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Experimental colon cancer

Cited by 149 publications

References 90 publications

A predictive biomarker for altered 5‐fluorouracil pharmacokinetics following repeated administration in a rat model of colorectal cancer

A predictive biomarker for altered 5‐fluorouracil pharmacokinetics following repeated administration in a rat model of colorectal cancer

Chemopreventive Effects of Nonsteroidal Anti-Inflammatory Drugs in the Membrane Lipid Composition and Fluidity Parameters of the 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis in Rats

Cruciferous vegetables and glutathione: Their effects on colon mucosal glutathione level and colon tumor development in rats induced by DMH

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