The influence of selenium and caffeine on chemical carcinogenesis in rats, mutagenesis in bacteria, and unscheduled DNA synthesis in human lymphocytes.

The influence of sodium selenite (Na2SeO3) and caffeine on chemical carcinogenesis induced in rats by diethylnitrosamine (DEN), N-nitrosomorpholine (NM), andN-methyl-N-nitro-N-nitrosoguanidine (MNNG) was investigated. A dose-dependent inhibitory effect of Na2SeO3 (l-10 ppm) on hepatocarcinogenesis induced by DEN was demonstrated. Na2SeO3 also increased the latency period for stomach tumor formation in rats treated with MNNG. Combined treatment of rats with Na2SeO3 plus vitamin C added to the diet resulted in a slight inhibition of NM-induced liver carcinogenesis. Supplementation of diet with Na2SeO3 plus butylated hydroxytoluene, vitamin C, and vitamin E did not reveal any additive inhibitory effect compared to the inhibitory effect of Na2SeO3 given alone. Caffeine (600 rag/L) reduced the number of liver tumors induced in rats by DEN. Preliminary experiments have indicated that combined treatment of rats with selenium and caffeine could result in more effective inhibition of DEN-induced liver carcinogenesis.Further experiments are being conducted to study the influence of selenium and caffeine on mutagenic activity of 1-methyl-l-nitrosourea (MNU) inSalmonella typhimurium TA 1535. The pretreatment of bacteria cells with Na2SeO3 (3-10 p.g/mL) increased the mutagenic response of bacteria to MNU. A synergistic stimulation of mutagenic activity of MNU was observed in bacteria pretreated simultaneously with Na2SeO3 and caffeine.In addition the influence of Na2SeO3 on UDS induced by DEN in human lymphocytes was investigated. The trace element inhibited the UDS up to 82%.The possible role of potentiation by NazSeO3 of the cell killing effect of DEN in inhibition of liver carcinogenesis was discussed.