Melatonin and colon carcinogenesis. IV. Effect of melatonin on proliferative activity and expression of apoptosis-related proteins in the spleen of rats exposed to 1,2-dimethylhydrazine

The suppression of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis by melatonin was previously demonstrated. The objective of the present wor k was to evaluate histologically and immunohistochemically the splenic immu ne response to the induced cancer and to melatonin. Spleens from rats, eith er untreated, injected with DMH, fed with melatonin or treated with both ca rcinogen and melatonin, were studied. The exposure to the carcinogen and th e consequential carcinogenesis resulted in splenic changes that reflected t he insufficiency of the immune response, as manifested in significant reduc tion of the white pulp and the simultaneous expansion of the red pulp. The effects of melatonin on most splenic components were inverse to those of DM H. The anti-carcinogenic properties of melatonin were evidenced from the re versal of the inhibitory effects of DMH, especially when the densities of l ymphocytes in different parts of the spleen were compared. The combined tre atment of the rats with DMH and melatonin resulted in the expansion of the splenic zones by 106% to 125%, compared to those from DMH-treated rats, and the numbers of CD8(+) lymphocytes and Fas-positive cells increased sharply . Therefore we conclude that anti-carcinogenic effects of melatonin are rel ated to activation of several elements of the host's lymphatic system.