Abstract
Denervation of the colon is protective against the colon cancer; however, the mechanisms involved are unknown. We tested the hypothesis that the denervated colonic mucosa could be less responsive to the action of the chemical carcinogen dimethylhydrazine (DMH). Three groups of 32 male Wistar rats were treated as follows: group 1 (G1) had the colon denervated with 0.3 mL 1.5 mM benzyldimethyltetradecylammonium (benzalkonium chloride, BAC); G2 received a single ip injection of 125 mg/kg DMH; G3 was treated with BAC + the same dose and route of DMH. A control group (Sham, N = 32) did not receive any treatment. Each group was subdivided into four groups according to the sacrifice time (1, 2, 6, and 12 weeks after DMH). Crypt fission index, ss-catenin accumulated crypts, aberrant crypt foci, and cell proliferation were evaluated and analyzed by ANOVA and the Student t-test. G3 animals presented a small number of aberrant crypt foci and low crypt fission index compared to G2 animals after 2 and 12 weeks, respectively. From the second week on, the index of ss-catenin crypt in G3 animals increased slower than in G2 animals. From the 12th week on, G2 animals presented a significant increase in cell proliferation when compared to the other groups. Colonic denervation plays an anticarcinogenic role from early stages of colon cancer development. This finding can be of importance for the study of the role of the enteric nervous system in the carcinogenic process.
Highlights
It has been reported that constipation may be an important factor in the pathogenesis of colorectal cancer because it prolongs the contact of colonic cells with metabolic and dietary carcinogens [1]
We tested this hypothesis by analyzing the effects of the carcinogen 1,2-dimethylhydrazine (DMH) on histological parameters that are believed to precede the development of chemically induced tumors in www.bjournal.com.br rodents, i.e., the formation of aberrant crypt foci (ACF), the crypt fission index (CFi), and the presence of ß-catenin accumulated crypts (BCAC)
Twelve weeks after DMH injection the group 2 (G2) animals showed a higher CFi than the other experimental groups, which were similar to one another (Figure 3)
Summary
It has been reported that constipation may be an important factor in the pathogenesis of colorectal cancer because it prolongs the contact of colonic cells with metabolic and dietary carcinogens [1]. One challenging hypothesis to explain this phenomenon is that the megacolon mucosa is less responsive to the action of chemical carcinogens and less favorable to the development of tumors. In this experiment, we tested this hypothesis by analyzing the effects of the carcinogen 1,2-dimethylhydrazine (DMH) on histological parameters that are believed to precede the development of chemically induced tumors in www.bjournal.com.br rodents, i.e., the formation of aberrant crypt foci (ACF), the crypt fission index (CFi), and the presence of ß-catenin accumulated crypts (BCAC)
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