Potential role of melatonin in DNA damage caused by nitrosourea-induced mammary carcinogenesis

Mammary carcinogenesis was induced in female Sprague-Dawley rats by exposure to N-methyl-N-nitrosourea (NMU). Animals were kept under constant light conditions to arrest endogenous melatonin synthesis and were fed the same melatonin dosage, since nitrosourea exposure may also induce cellular injury, especially with extensive proliferative activity. The pro-apoptotic effects of the biogenic amine, melatonin, on rat whole blood leukocytes were assessed by alkaline single cell gel electrophoresis (comet) assay. Potential induction of stress due to animal immobilization and its additional effect on DNA damage was studied. The parameters relevant to the degree of DNA damage in groups with chemocarcinogen treatment demonstrated no significant effects as a result of the immobilization. A significant increase in DNA damage after melatonin treatment in NMU-induced carcinogenesis confirms its involvement in the activation of apoptosis.