Epigenetic effects of N-methyl-N′-nitro-N-nitrosoguanidine on Kazakh esophageal epithelial cells

Epigenetic change is a key factor for esophageal cancer progression. This study shows that upon exposure of primary cultures of human esophageal epithelial cells obtained from people of the Kazakh nationality in China to N-methyl-N′-nitro-N-nitrosoguanidine at concentrations of 0.75, 1.50, and 3.00 mg/L, (1) cell proliferation was inhibited, the percentages of cells in the G₀ and G₁ phases declined, and those in the S and G₂ + M phases increased at all concentrations, while apoptosis rates increased at medium and high concentrations; (2) the content of DNA-methyltransferases 3a and 3b and the activities of DNA-methyltransferase 1 and DNA-methyltransferase 3a increased at all concentrations while the content of DNA-methyltransferase 1 and the activity of DNA-methyltransferase 3b were increased only at the high concentration; (3) messenger RNA and protein levels of DNA-methyltransferases 1, 3a, and 3b were increased at all concentrations. Obviously, N-methyl-N′-nitro-N-nitrosoguanidine in the low mg/L range can inhibit the proliferation of normal Kazakh esophageal epithelial cells, can cause cell cycle arrest in the S and G₂ + M phases, promote apoptosis, and increase the activities of DNA-methyltransferases 1, 3a, and 3b.