Melatonin and colon carcinogenesis - III. Effect of melatonin on proliferative activity and apoptosis in colon mucosa and colon tumors induced by 1,2-dimethylhydrazine in rats

Forty-eight two-month-old outbred female LIO rats were injected weekly with a single dose of 1,2-dimethylhydrazine (DMH; 21 mg/kg of body weight) admi nistered s.c. for 15 consecutive weeks. From the day of the ist injection o f the carcinogen the part of rats were given five days a week during the ni ght time (from 18.00 h to 08.00 h) melatonin dissolved in tap water, 20 mg/ l. 10 rats were treated similaly with solvents and served as control. The e xperiment was terminated 6 months after the first injection of the carcinog en. Colon tumors (mainly adenocarcinomas) developed in a hundred percent of rats exposed both to DMH or to DMH plus melatonin. However, descending col on carcinomas were observed in 65 % of rats exposed to DMH plus melatonin a gainst 100 % in those exposed to DMH alone (p < 0.01). The multiplicity of colon tumors was also reduced in rats under the influence of melatonin. Thi s effect is correlated with the significant inhibitory effect of the pineal hormone on mitotic index and with stimulating effect of melatonin on the r elative number of apoptotic cells (TUNEL-method) in colon tumors. Long-term treatment with melatonin was followed also by the decrease in the area of lymphoid infiltrates in the colon mucosa of tumor-bearing rats.