Melatonin and colon carcinogenesis: I. Inhibitory effect of melatonin on development of intestinal tumors induced by 1,2-dimethylhydrazine in rats |
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Authors: | Anisimov VN; Popovich IG; Zabezhinski MA |
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Institution: | Laboratory of Experimental Tumors, N.N. Petrov Research Institute of Oncology, St Petersburg, Russia. |
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Abstract: | The effect of pineal indole hormone melatonin on colon carcinogenesis was
firstly studied in rats. Two-month-old outbred female LIO rats were weekly
exposed 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 single
dose of 21 mg/kg of body weight. From the day of the first injection of the
carcinogen DMH, the rats from groups 2 (experiments 1 and 2) were given
melatonin 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 months
after the first injection of DMH. In both experiments the majority of
tumors were localized in the descending colon. Tumors of the small
intestines developed only in rats from experiment 1. Total incidence of
colon tumors as well as tumors in different parts of the colon and the mean
number of tumors per rat were much higher in rats from both groups in
experiment 1 than that in rats from experiment 2. In experiment 1 melatonin
failed to influence the total incidence of colon tumors. However, incidence
of carcinomas in the ascending colon was significantly reduced (P <
0.01). The multiplicity 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 experiment, 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 rats from group 2 was higher than that of group 1.
Treatment with melatonin 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 decrease 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 DMH-induced colon carcinogenesis was much more expressed
than that in experiment 1. Thus, in group 1 the incidence of total colon
tumors, ascending and descending colon tumors, was significantly decreased
in comparison with group 2; also melatonin reduced the number of tumors per
rat in the ascending and descending colon. The number of colon tumors that
invaded 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. The
number of large size tumors in the ascending and descending colon was
decreased whereas the number of small size tumors (<10 mm2) was
increased in those parts of the colon that were under the influence of
melatonin in experiment 2. Thus, our results demonstrate the inhibitory
effect of melatonin on intestinal carcinogenesis induced by DMH in rats.
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