Dose-dependent inhibitory effect of melatonin on carcinogenesis induced by benzo[a]pyrene in mice.

Three-month-old Swiss-derived SHR mice were subcutaneously injected with 2 mg of benzo[a]pyrene (BP) dissolved in 0.1 ml of olive oil. After the injections of the carcinogen two groups of mice were given melatonin with night drinking water at the doses of 2 mg/l or 20 mg/l and one group of mice was not treated with melatonin and served as a PB-control. At the 28th week after the carcinogen administration the experiment was stopped and animals were sacrificed. The results show that melatonin treatment inhibits BP-induced carcinogenesis, decreases the incidence of subcutaneous sarcomas, increases their latency and survival of mice. The malone dialdehyde (MDA) level in the serum of BP-induced tumor-bearing mice was increased by 2.6 times (p < 0.01) and in the tumors was increased by 11.1% (p < 0.01) as compared to intact control mice. Treatment with melatonin significantly decreased the MDA level both in the serum and tumor tissue. The activity of catalase in the serum of BP-induced tumor-bearing mice was increased by 12.1% as compared to the intact control mice (p < 0.01) and was unchanged in the tumor tissue. Treatment with melatonin at the dose of 2 mg/l significantly decreased activity of catalase in the serum (by 31.7%, p < 0.01) and in the tumor tissue (by 2.6 times, p < 0.01) as compared to the animals treated with BP alone. Thus, it wose shown for the first time an inhibitory effect of melatonina on malignancies of mesenchymal origin. Lower dose of melatonin appeared to be more effective in the inhibition of lipid peroxidation and tumorigenesis induced by chemical carcinogen than a higher one.