Melatonin and colon carcinogenesis: I. Inhibitory effect of melatonin on development of intestinal tumors induced by 1,2-dimethylhydrazine in rats

The effect of pineal indole hormone melatonin on colon carcinogenesis wasfirstly studied in rats. Two-month-old outbred female LIO rats were weeklyexposed to 15 (experiment 1, groups 1 and 2) or to five (experiment 2,groups 1 and 2) s.c. injections of 1,2-dimethylhydrazine (DMH) at a singledose of 21 mg/kg of body weight. From the day of the first injection of thecarcinogen DMH, the rats from groups 2 (experiments 1 and 2) were givenmelatonin five days a week during the night-time (from 18:00 h to 8:00 h),dissolved in tap water at 20 mg/l. The experiment was finalized in 6 monthsafter the first injection of DMH. In both experiments the majority oftumors were localized in the descending colon. Tumors of the smallintestines developed only in rats from experiment 1. Total incidence ofcolon tumors as well as tumors in different parts of the colon and the meannumber of tumors per rat were much higher in rats from both groups inexperiment 1 than that in rats from experiment 2. In experiment 1 melatoninfailed to influence the total incidence of colon tumors. However, incidenceof carcinomas in the ascending colon was significantly reduced (P <0.01). The multiplicity of total colon tumors per rat, as well as the meannumber of tumors, ascending and descending colon per rat, was alsodecreased under the influence of melatonin (group 2 vs group 1, P <0.01). In the same experiment, melatonin slightly decreased the depth oftumor invasion and increased number of highly differentiated coloncarcinomas induced by DMH. The percentage of small tumours in thedescending colon among rats from group 2 was higher than that of group 1.Treatment with melatonin was also followed by a decrease in themultiplicity of DMH- induced tumors of the duodenum (group 2 vs group 1, P< 0.05) and by a decrease in the incidence of jejunum and ileum tumors(group 2 vs group 1, P < 0.05). In experiment 2, the inhibitory effectof melatonin on DMH-induced colon carcinogenesis was much more expressedthan that in experiment 1. Thus, in group 1 the incidence of total colontumors, ascending and descending colon tumors, was significantly decreasedin comparison with group 2; also melatonin reduced the number of tumors perrat in the ascending and descending colon. The number of colon tumors thatinvaded only mucosa was significantly higher in group 2 than in group 1, P< 0.05. The ratio of highly differentiated tumors was increased (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 group 3. Thenumber of large size tumors in the ascending and descending colon wasdecreased whereas the number of small size tumors (<10 mm2) wasincreased in those parts of the colon that were under the influence ofmelatonin in experiment 2. Thus, our results demonstrate the inhibitoryeffect of melatonin on intestinal carcinogenesis induced by DMH in rats.