Carcinogenesis, Vol 19, 1591-1596, Copyright © 1998 by Oxford University Press
LY Fong, JL Farber and PN Magee
Previous work has shown that sustained increased and decreased cell
proliferation, induced by dietary zinc deficiency and caloric restriction
respectively, influence the course of N- nitrosomethylbenzylamine
(NMBA)-induced esophageal carcinogenesis in rats. The present study
considered whether the increased cell proliferation and esophageal tumor
incidence induced by zinc deficiency are reversed upon zinc replenishment.
Weanling rats were maintained initially on a deficient diet containing 4
p.p.m. zinc. After 5 weeks, carcinogen-treated animals were given six
intragastric doses of NMBA (2 mg/kg twice weekly). Controls were untreated.
After the second NMBA dose, the rats were divided into three dietary
groups. One group was continued on the deficient diet, while the other two
groups were switched to diets containing either 75 or 200 p.p.m. zinc, with
half of the members in each group fed ad libitum and half pair-fed with
deficient rats. NMBA-untreated controls were similarly replenished. At
various time points, esophageal cell proliferation was assessed in five
animals from each group by immunohistochemical detection of cells in S
phase, with in vivo 5-bromo-2'deoxyuridine labeling. At 11 weeks after the
first dose, esophageal tumor incidence was greatly reduced, from 100% in
the deficient group to 26 and 14% respectively in the replenished groups
fed ad libitum 75 and 200 p.p.m. zinc and to 14 and 11% respectively in the
replenished groups pair-fed 75 and 200 p.p.m. zinc. In addition, the number
of tumors per esophagus was reduced from 9.93 +/- 4.25 in deficient rats,
to a range of 0.11 +/- 0.31-0.30 +/- 0.54 in replenished animals. Following
zinc replenishment, esophageal cell proliferation, as measured by labeling
index (LI), the number of labeled cells and the total number of cells, was
markedly decreased in NMBA-untreated and -treated esophagi as compared with
those in corresponding deficient esophagi. Thus, the esophageal cell
proliferation induced by zinc deficiency is reversed by zinc replenishment
and replenished animals have a markedly lower incidence of esophageal
tumors.
ARTICLES
Zinc replenishment reduces esophageal cell proliferation and N- nitrosomethylbenzylamine (NMBA)-induced esophageal tumor incidence in zinc-deficient rats
Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA. l_fong@hendrix.jci.tju.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K.-S. Park, N.-G. Lee, K.-H. Lee, J. T. Seo, and K.-Y. Choi The ERK pathway involves positive and negative regulations of HT-29 colorectal cancer cell growth by extracellular zinc Am J Physiol Gastrointest Liver Physiol, December 1, 2003; 285(6): G1181 - G1188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Y. Y. Fong, V. T. Nguyen, and J. L. Farber Esophageal Cancer Prevention in Zinc-Deficient Rats: Rapid Induction of Apoptosis by Replenishing Zinc J Natl Cancer Inst, October 17, 2001; 93(20): 1525 - 1533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. P. Dragan, W. R. Bidlack, S. M. Cohen, T. L. Goldsworthy, G. C. Hard, P. C. Howard, R. T. Riley, and K. A. Voss Implications of Apoptosis for Toxicity, Carcinogenicity, and Risk Assessment: Fumonisin B1 as an Example Toxicol. Sci., May 1, 2001; 61(1): 6 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Y. Y. Fong, V. T. Nguyen, J. L. Farber, K. Huebner, and P. N. Magee Early Deregulation of the p16ink4a-Cyclin D1/Cyclin-dependent Kinase 4-Retinoblastoma Pathway in Cell Proliferation-driven Esophageal Tumorigenesis in Zinc-deficient Rats Cancer Res., August 1, 2000; 60(16): 4589 - 4595. [Abstract] [Full Text]
|
|