MELATONIN AND COLON CARCINOGENESIS .1. INHIBITORY EFFECT OF MELATONINON DEVELOPMENT OF INTESTINAL TUMORS INDUCED BY 1,2-DIMETHYLHYDRAZINE IN RATS

The effect of pineal indole hormone melatonin on colon carcinogenesis was firstly studied in rats, Two-month-old outbred female LIO rats wer e weekly exposed to 15 (experiment 1, groups 1 and 2) or to five (expe riment 2, groups I and 2) s.c. injections of 1,2-dimethylhydrazine (DM H) at a single dose of 21 mg/kg of body weight, From the day of the fi rst injection of the carcinogen DMH, the rats from groups 2 (experimen ts 1 and 2) were given melatonin five days a week during the night-tim e (from 18:00 h to 8:00 h), dissolved in tap mater at 20 mg/l, The exp eriment was finalized in 6 months after the first injection of DMH. In both experiments the majority of tumors were localized in the descend ing colon, Tumors of the small intestines developed only in rats from experiment 1, Total incidence of colon tumors as well as tumors in dif ferent parts of the colon and the mean number of tumors per rat mere m uch higher in rats from both groups in experiment 1 than that in rats from experiment 2, In experiment 1 melatonin failed to influence the t otal incidence of colon tumors, However, incidence of carcinomas in th e ascending colon was significantly reduced (P < 0.01), The multiplici ty of total colon tumors per rat, as well as the mean number of tumors , ascending and descending colon per rat, was also decreased under the influence of melatonin (group 2 vs group 1, P < 0.01), In the same ex periment, melatonin slightly decreased the depth of tumor invasion and increased number of highly differentiated colon carcinomas induced by DMH, The percentage of small tumours in the descending colon among ra ts from group 2 was higher than that of group 1, Treatment with melato nin was also followed by a decrease in the multiplicity of DMH-induced tumors of the duodenum (group 2 vs group 1, P < 0.05) and by a decrea se in the incidence of jejunum and ileum tumors (group 2 vs group 1, P < 0.05), In experiment 2, the inhibitory effect of melatonin on DR IH -induced colon carcinogenesis was much more expressed than that in exp eriment I, Thus, in group 1 the incidence of total colon tumors, ascen ding and descending colon tumors, was significantly decreased in compa rison with group 2; also melatonin reduced the number of tumors per ra t in the ascending and descending colon, The number of colon tumors th at invaded only mucosa was significantly higher in group 2 than in gro up 1, P < 0.05, The ratio of highly differentiated tumors was increase d (P < 0.05) and the ratio of low-differentiated tumors was decreased (P < 0.05) in rats exposed to melatonin (group 4) as compared with gro up 3, The number of large size tumors in the ascending and descending colon was decreased whereas the number of small size tumors (< 10 mm(2 )) was increased in those parts of the colon that mere under the influ ence of melatonin in experiment 2, Thus, our results demonstrate the i nhibitory effect of melatonin on intestinal carcinogenesis induced by DMH in rats.