Impact of dihydropyrrol derivative on the normal colonic mucosa of DMH-induced colon cancer rats compared with 5-fluorouracil

• Published in: Experimental oncology Vol. 35; no. 1; p. 25
• Main Authors: Kuznietsova, H M, Ogloblya, O V, Rybalchenko, V K
• Format: Journal Article
• Language: English
• Published: Ukraine 01-03-2013
• Subjects: Animals; Antineoplastic Agents - pharmacology; Benzothiazoles - therapeutic use; Cell Proliferation; Cell Transformation, Neoplastic - drug effects; Colonic Neoplasms - chemically induced; Colonic Neoplasms - drug therapy; Colonic Neoplasms - prevention & control; Dimethylhydrazines; Fluorouracil - pharmacology; Intestinal Mucosa - drug effects; Male; Pyrroles - pharmacology; Pyrrolidinones - therapeutic use; Rats; Rats, Wistar
• ISSN: 1812-9269

To compare the effects of cytostatic compound dihydropyrrol derivative (D1, 5-amyno-4-(1,3-benzothyazol-2-yl)-1-(3-methoxyphenyl)-1,2-dihydro-3Н-pyrrol-3-one) and 5-fluorouracil (5-FU) on the normal colonic mucosa of tumor-bearing rats and to estimate the relationships between proliferation of normal colonic mucosa and tumor growth parameters.
1,2-dimethylhydrazine (DMH) carcinogenic model was used. Male Wistar rats were treated by dimethylhydrazine (20 mg/kg of body weight (b.w.) weekly) for 20 weeks, by D1 (2.3 mg/kg of b.w. daily) for 7 or 27 weeks, and by 5-FU (45 mg/kg of b.w. weekly) for 7 weeks. The number of tumor and tumor total area in dissected colon, mitotic and crypt fission indices in surrounding colon mucosa were measured and correlations between these parameters were computed.
The number of tumor node and tumor total area under the influence of D1 and 5-FU were decreased by 40-54%. D1 administration has resulted in the more gentle effect on surrounding healthy colon mucosa comparing to 5-FU, particularly, on vascular bed and proliferative activity. The changes in colon mucosa proliferative activity correlate with tumor growth parameters depending on the action of D1 or 5-FU.
D1 manifests the same antitumor activity but less toxicity comparing to 5-FU that allow to suggest its possible use as an anticancer mean. Obtained correlations could be useful for better understanding of the processes preceeding the malignant transformation and their pharmaceutical correction.