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 w ork showed that zinc deficiency and its associated increased esophageal cel l proliferation were of paramount importance in esophageal tumor developmen t in the NMBA-rat model. However, there has been no report concerning zinc deficiency and NMBA-induced esophageal tumor formation in mice. In this stu dy, 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 intr agastric doses of NMBA (2 mg/kg; twice weekly for 3 weeks). The animals wer e 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% respec tively, in the esophagus, forestomach and squamocolumnar junction with the glandular stomach (SCJ), as compared to 17, 39, and 67% in the correspondin g tissue of zinc-sufficient mice. The difference between the two dietary gr oups was significant at P < 0.02 for the esophagus, and P < 0.001 for the f orestomach and the SCJ. BrDU labeling revealed that the esophageal labeling index and the number of labeled cells were increased by zinc deficiency. T hese results support a role of increased cell proliferation in esophageal c arcinogenesis in the mouse. (C) 1999 Elsevier Science Ireland Ltd. All righ ts reserved.