[661] 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).

Table 1. Effect of Zn supplementation on NMBA-induced tumor development in four mouse strains

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

Table 2. Histopathological analysis of forestomach lesions

Genotype	Treatment	# Mice	Normal	Mild hyperplasia	Severe hyperplasia	hyperplasia w. dysplasia	Carcinoma
B6*	no Zn	24	0	1	19	11	4
	Zn	29	3	17	8	6	0
Fhit-/-Nit1-/-*	no Zn	24	0	2	16	8	4
	Zn	26	2	6	17	3	0
Chi square test (Zn vs no Zn): p=0.003 in B6 and p=0.002 in Fhit-/-Nit1-/- mice.

Conclusions: Zn supplementation significantly reduced tumor burdens in mice. When Zn supplementation was begun at 7 weeks after the final carcinogen dose, the reduction in tumor burden was the same as observed when supplementation began immediately after carcinogen dosing, suggesting that Zn supplementation may affect tumor progression rather than initiation, and supporting the hypothesis that Zn has a role in tumor prevention that should be more thoroughly examined and defined in preclinical models.
Category: Gastrointestinal

Monday, February 28, 2011 1:00 PM

Poster Session II # 91, Monday Afternoon