Experimental Colon Tumorigenesis Induced by 1,2 Dimethylhydrazine in Balb/C Mice

Karaca, Oğuz; Ertekın, Tolga; Canöz, Özlem; Hacialioğullari, Mehtap; Ekinci, Nihat; Elmalı, Ferhan; Ülger, Harun

doi:10.5336/medsci.2008-10117

Cited by 5 publications

(8 citation statements)

References 17 publications

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“…It has been reported that DMH induces mutations predominantly in the colon, as compared to the small intestine (Newell and Heddle, 2004). We have previously shown that s.c. injection of 20 mg/kg/week DMH during the 12 weeks caused 100% epithelial dysplasia at weeks 6 and 100% carcinoma at week 18 after the last injection of DMH (Karaca et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Eighteen weeks after the last injection, all mice were killed with an overdose of ketamine. Our previous work showed that s.c. injection of DMH 20 mg/kg/week during the 12 weeks caused 100% carcinoma at week 18 after last injection (Karaca et al, 2010). After the death of the animal, the abdomen was opened and approximately 7–8-cm long large intestine was cut between cecum and anal canal by a scissors.…”

Section: Methodsmentioning

confidence: 99%

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Influence of gilaburu (Viburnum opulus) juice on 1,2-dimethylhydrazine (DMH)-induced colon cancer

et al. 2012

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In this study, the effects of gilaburu (Viburnum opulus) juice on colon tumorogenesis were investigated. Eight weeks old Balb-C male mice received subcutaneous injections of 1,2-dimethylhydrazine (DMH) (20 mg/kg body weight) once a week for 12 weeks. Both the sham control (group 1) and the DMH control (group 2) groups received drinking water alone, whereas the mice of groups 3 and 4 received gilaburu juice for 30 weeks (started with first DMH injection) and for 18 weeks (started after last DMH injection), respectively. Eighteen weeks after the last DMH injection, all mice were killed and the histogenesis of colon tumors was investigated from the paraffin-embedded sections of colon, which were stained with hematoxylin-eosin. The sites and incidences of tumoral lesions (low-grade dysplasia, high-grade dysplasia, intramucosal carcinoma and invasive carcinoma) were analyzed and compared with control. The results showed that the body weights of the mice were similar in all the groups. No tumoral lesions were found in group 1. Colon tumors developed in all DMH-treated mice (groups 2, 3 and 4). In these groups, the greatest numbers of tumor lesions were detected in the distal colon, followed by the mid-colon and only a few in the proximal colon. There was a reduction in the mean total number of tumor lesion in groups 3 (8.5) and 4 (8.3), when compared to group 2 (11.3). The incidence of invasive carcinoma in group 3 was significantly lower than group 2 (p < 0.05). On the basis of these results, we conclude that gilaburu juice may be useful for the prevention of colon cancer at the initiation stage.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Influence of gilaburu (Viburnum opulus) juice on 1,2-dimethylhydrazine (DMH)-induced colon cancer

et al. 2012

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“…In our previous study, we found that subcutaneous injection of 20 mg/kg/week of DMH during the 12 weeks caused 100% epithelial dysplasia at the following 6th week and 85% high grade dysplasia at the following 12th week after last injection (Karaca et al, 2010). The phase, where 85% high grade dysplasia was seen, was a critical period in terms of precancerous conditions.…”

Section: Treatment Protocolmentioning

confidence: 91%

Effect of endostatin on 1,2-dimethylhydrazine-induced colon tumor in mice

et al. 2011

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Endostatin, one of the most potent negative regulators of angiogenesis, is naturally occurring as an inhibitor of angiogenesis capable of inhibiting tumor growth and their metastases. We aimed to investigate the in vivo activities of low dose of recombinant human endostatin on 1,2-dimethylhydrazine (DMH)-induced mice colon cancer. Thirty male Balb-c mice were injected with DMH (20 mg/kg/week) subcutaneously once a week for 12 weeks to induce colon cancer. Twelve weeks after the last DMH injection, 7 µg rh-endostatin was injected every day for 6 weeks. The animals were killed after 30 weeks for histopathological examination. The weight of the animals, tumor inhibition rates, death rates and the distribution of the lesions in colon were evaluated after the mice were killed. The mean colonic lesions incidence in single tumor bearing mice was 11 ± 4.0 in those treated with DMH and 8.1 ± 3.7 in those treated with endostatin. When we look at the distribution of lesions in the colon, they occurred in the distal colon. At the end of our study, we noticed that the number of lesions decreased by 25% in the group of endostatin, considering the number of the lesions in the group of DMH. But there was no statistical difference between the mice treated with endostatin and those treated with DMH. It will be very significant to identify endostatin therapeutic effects as long as proper dose of endostatin is administrated at the proper time, duration and proper tumor model.

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“…In our previous study using the DMH carcinogenic model, different durations of treatment free intervals were used. We found that subcutaneous injection of 20 mg/kg/week DMH during 12 weeks caused 100% epithelial dysplasia in the following 6th week (Karaca et al, 2010). The phase, at which 100% epithelial dysplasia was seen, was a critical period in terms of precancerous conditions.…”

Section: Methodsmentioning

confidence: 96%

“…It was then opened longitudinally using scissors, washed with phosphate-buffered saline and the mucosal surface examined for gross pathology (number and distribution of the neoplasms). Following macroscopic examination, the colon tissues were prepared for histopathologic examination according to the Swiss-roll technique (Karaca et al, 2010; Moolenbeek and Ruıtenberg, 1981; Reilly and Kirsner, 1965). This technique allows the entire intestinal mucosa to be examined efficiently.…”

Section: Methodsmentioning

confidence: 99%

Effect of angiostatin on 1,2-dimethylhydrazine-induced colon cancer in mice

et al. 2012

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Antiangiogenic therapy is supposed to be an attractive approach for antitumor treatment. Human plasminogen-derived angiostatin K1-3 is one of the most potent antiangiogenic agents known currently. However, it is unclear whether angiostatin has got protective effects on colon cancer. So we investigated the protective effects of angiostatin on 1,2-dimethylhydrazine (DMH)-induced colon cancer in mice. Thirty Balb/C male mice, weighing 25-30 g and 8 weeks of age, were used. Twenty of the mice were treated with DMH subcutaneously (20 mg/kg) once a week for 12 weeks. Six mice died during the DMH injection and surviving mice were divided into two groups (7 mice in DMH and 7 mice in DMH + angiostatin groups). In the angiostatin group, 6 weeks after the last DMH injection the animals were first treated with angiostatin (20 μg/mouse) intraperitoneally and then subcutaneously every 48 h (5 μg/mouse) throughout a period of 12 weeks. The animals were killed after 30 weeks for histopathological examination. When we look at the distribution of lesions in the colon, they mainly occurred in the distal colon. The incidence of mean colonic lesions in a tumor-bearing mouse was 9.85 ± 4.91 in those treated with DMH and 8.71 ± 3.49 in those treated with angiostatin. The incidence of colon tumors was not significantly affected by low dose of angiostatin, and we noticed that the number of lesions decreased by 12% in DMH + angiostatin group compared to the number of the lesions in DMH group, but this decrease was not statistically significant (p > 0.05). The administration period of angiostatin corresponds to the precancerous period and the reduction in the number of lesions could be important for the protective function of angiostatin in DMH + angiostain group. We assume that therapeutic effects of angiostatin are related to its doses, route of administration, frequency and administration period. In addition, we believe that combination of high doses of angiostatin with radiation, gene therapy or chemotherapy might be successful in proper tumor model.

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Experimental Colon Tumorigenesis Induced by 1,2 Dimethylhydrazine in Balb/C Mice

Cited by 5 publications

References 17 publications

Influence of gilaburu (Viburnum opulus) juice on 1,2-dimethylhydrazine (DMH)-induced colon cancer

Influence of gilaburu (Viburnum opulus) juice on 1,2-dimethylhydrazine (DMH)-induced colon cancer

Effect of endostatin on 1,2-dimethylhydrazine-induced colon tumor in mice

Effect of angiostatin on 1,2-dimethylhydrazine-induced colon cancer in mice

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