Dietary zinc deficiency enhances esophageal cell proliferation and N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumor incidence in C57BL/6 mouse.

The effect of zinc deficiency on N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumor formation in rats has been well documented. Our previous work showed that zinc deficiency and its associated increased esophageal cell proliferation were of paramount importance in esophageal tumor development in the NMBA-rat model. However, there has been no report concerning zinc deficiency and NMBA-induced esophageal tumor formation in mice. In this study, weanling C57BL/6 mice were fed ad libitum with either a zinc-sufficient or a zinc-deficient diet containing 3-4 ppm of zinc, and received six intragastric doses of NMBA (2 mg/kg; twice weekly for 3 weeks). The animals were sacrificed 46 weeks later after in vivo bromodeoxyuridine (BrDU) labeling followed by immunohistochemical detection of cells in S-phase. At 46 weeks, the tumor incidences in zinc-deficient mice were 57, 100, and 100% respectively, in the esophagus, forestomach and squamocolumnar junction with the glandular stomach (SCJ), as compared to 17, 39, and 67% in the corresponding tissue of zinc-sufficient mice. The difference between the two dietary groups was significant at P < 0.02 for the esophagus, and P < 0.001 for the forestomach and the SCJ. BrDU labeling revealed that the esophageal labeling index and the number of labeled cells were increased by zinc deficiency. These results support a role of increased cell proliferation in esophageal carcinogenesis in the mouse.