INDUCTION OF S-METOLACHLOR PRENEOPLASTIC LIVER LESION IN RAT INITIATED CARCINOGENESIS BY NITROSODIETHYLAMINE

Bahley Ye., Nedopytanska N., Lisovska V., Reshavska Ye., Tkachenko L.

PATHOMORPHOLOGY

Scentific article

A significant place among carcinogens of potential initiators of carcinogenesis in humans belongs to nitro so compounds. S-metolachlor widely used in growing crops. Objective. To study the effect of S-metolachlor on the development of preneoplastic liver lesions in carcinogenesis initiated by nitrosodiethylamine (NDEA). Object and methods. S-metolachlor. The experiments were performed on male Wistar Han rats, were given a single intraperitoneum injection of NDEA, 200 mg/kg, for initiated carcinogenesis. Two weeks after injection the of NDEA, S-metolachlor was administered by intragastrically to the animals of the experimental groups at doses of 1.5; 15 and 150 mg/kg bw for 8 weeks. Hepatectomy was performed 3 weeks after the start of the experiment. Animals from the negative control group received water, and positive – phenobarbital. During the experiment, clinical studies were conducted. Evaluated – the general condition of the animals, their weight and its increase. After necropsy, a macroscopic and histological examination was performed. Liver sections were analyzed for γ-glutamyltranspeptidase (γ-GTP) expression. The numbers and areas of γ-GTP positive foci, which are biomarker for preneoplastic liver lesion, were determined by a special computer program. Results. Clinical signs of toxic effects of S-metolachlor in rats, have not been established. Changes in liver mass in animals exposed to S-metolachlor were not detected. In rats treated with phenobarbital, an increase in the relative weight of the liver was found. An increase in the development of γ-GTP positive foci in the liver of animals treated with medium and high doses of S-metolachlor and phenobarbital was found. In animals that received a dose of 1.5 mg/kg S-metolachlor, the effect was absent. Conclusion. S-metolachlor induces the development of preneoplastic lesions, enhancing the proliferation of transformed hepatocytes, and thus has a promoter effect in liver carcinogenesis initiated by NDEA in rats. The threshold nature of this effect is shown.

carcinogenesis, NDEA, S-metolachlor, γ-glutamyltranspeptidase, proliferative processes, pre neoplastic lesions.

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«Bulletin of problems biology and medicine» Issue 2 Part 1 (150), 2019 year, 270-274 pages, index UDK 615.9:632.95:616-006

10.29254/2077-4214-2019-2-1-150-270-274