Dietary Zinc Inhibits N-Nitrosomethylbenzylamine-Induced Esophageal Carcinogenesis in Wild-Type and Tumor Suppressor-Deficient Mouse Strains.
James Liu, Jin Sun, Xueliang Pan, Donald Quimby, Nicola Zanesi, Teresa Druck, Gerd P Pfeifer, Carlo M Croce, Louise Y Fong3, Kay Huebner. Ohio State University, Columbus; The City of Hope National Medical Center, Duarte, CA; Jefferson Medical College, Philadelphia, PA
Background: Zinc (Zn) deficiency in humans is associated with increased risk of developing esophageal cancer, and leads to carcinoma in the upper gastrointestinal tract in laboratory rodents. Previous studies have focused on effect of Zn replenishment in deficient rodents. In this study, we investigated the effect of Zn supplementation on carcinogenesis in Zn-sufficient mice.
Design: Wild type C57BL/6 (B6), Fhit-/-, Fhit-/-Nit1-/- and Fhit-/-Rassf1a-/- mice were used. All mice received N-nitrosomethylbenzylamine (NMBA) and half of each then received Zn supplementation. 14-16 weeks final NMBA administration, mice were sacrificed and tumors in forestomach analyzed.
Results: The number of mice with tumors was significantly reduced in groups receiving Zn supplementation (Table 1). Histological analysis also showed significant decreases in severity of preneoplastic and neoplastic lesions in Zn-supplemented cohorts (Table 2).
|Genotype||Treatment||# mice||Tumors/mouse (mean ± SE)||# tumors of diameter/mouse|
|≤0.5 mm||∼1 mm||≥2 mm|
|B6||No Zn||24||7.0 ± 1.2||4.1||2.0||0.9|
|Zn||29||5.0 ± 0.7*||3.2||1.0||0.8|
|Fhit-/-||No Zn||34||8.0 ± 0.6||5.4||1.6||1.0|
|Zn||29||5.7 ± 1.0*||3.9||1.2||0.6|
|Fhit-/-Nit1-/-||No Zn||24||9.2 ± 1.6||4.5||3.2||1.5|
|Zn||26||5.3 ± 0.8*||3.2||1.3||0.9|
|Fhit-/-Rassf1a-/-||No Zn||26||9.1 ± 1.5||5.3||2.6||1.2|
|Zn||27||5.9 ± 0.5*||3.4||1.5||0.9|
|* Zn vs no Zn, p value <= 0.01|
|Genotype||Treatment||# Mice||Normal||Mild hyperplasia||Severe hyperplasia||hyperplasia w. dysplasia||Carcinoma|
|Chi square test (Zn vs no Zn): p=0.003 in B6 and p=0.002 in Fhit-/-Nit1-/- mice.|