Melatonin and colon carcinogenesis II. Intestinal melatonin-containing cells and serum melatonin level in rats with 1,2-dimethylhydrazine-induced colon tumors

Two-month-old outbred female LIO rats were injected weekly with a single do se of I,2-dimethylhydrazine (DMH; 21 mg/kg of body weight) administered s.c . for 15 consecutive weeks. From the day of the Ist injection of the carcin ogen the part of rats were given five days a week during the night time (fr om 18.00 h to 08.00 h) melatonin dissolved in tap water, 20 mg/l. The exper iment was terminated in 6 months after the first injection of the carcinoge n. The concentration of melatonin in the serum was estimated by radioimmuno assay in rats exposed to DMH alone or in intact control rats in the morning (between 10.00 and 11.00 hours) and night (between 24.00 and 01.00 hours) time. Number of melatonin-containing cells (M-cells) and their optical dens ity were estimated by immunohistology in normal mucosa of glandular stomach , duodenum, ileum and descending colon of tumor-bearing animals from groups exposed to DMH or DMH + melatonin. It was shown that serum melatonin level s in rats with colon tumors was increased as compared with controls. Howeve r there was no diurnal rhythm of serum melatonin of colon tumor-bearing ani mals as compared to intact controls. The number of M-cells was decreased in all tissues studied in rats with DMH-induced colon tumors in comparison to corresponding controls: by 2.0 times in stomach, by 1.8 time in duodenum, by 1.3 times in ileum, and by 1.8 times in colon. In ileum and colon of rat s treated with DMH + melatonin the number of M-cells was similar to control level whereas in stomach and duodenum this number was significantly higher than that in rats treated with DMH alone, but less than in corresponding c ontrols. Relative content of melatonin in enterochromaffin cells of all par ts of gastrointestinal tract evaluated as optical density of the cells and was decreased in rats exposed with DMH alone in comparison to the controls and was normalized and similar to the norm level in rats treated with DMH melatonin. Thus, exogenous melatonin prevent a decrease in numbers of mela tonin-containing cells as was observed in gastrointestinal tract (GIT) of r ats exposed to DMH. This preventive action of melatonin correlated well wit h its anticarcinogenic effect.