Expression of Metallothionein after Administration of Aspirin, Vitamin C or Zinc Supplement in the DMH Induced Colon Carcinoma in Rat

Abstract

Background: Chemoprevention refers to the use of specificnatural or synthetic chemical agents to suppress the<br />development and progression to carcinoma. The purpose of this study was to assess the effect of aspirin, vitamin C<br />or zinc on the metallothionein (MT) mRNA gene expression as well as MT protein content byimmunohistochemistry<br />andradioimmunoassay (RIA) in 1, 2-dimethyl hydrazine (DMH) induced cancerous colonic tissuein rats. Methods:<br />Rats were randomly divided into three groups, group 1 (aspirin), group 2 (vitamin C) group 3 (zinc), each of which<br />was further sub divided into two groups and given subcutaneous injections of DMH (30 mg/kg body weight) twice a<br />week for 3 months and sacrificed at either 4 months (A-precancer model) or at 6 months (B-cancer model).The control<br />groups were administered 0.5 ml saline subcutaneously. All the 3 groups were simultaneouslyadministered aspirin,<br />vitamin Cor zinc supplement respectively from the beginning till the end of the study. Results: It was observed that<br />rats co-treated with aspirin, vitamin C or zinc resulted in a significant increase in the colonic MT mRNA expression in<br />the precancer and cancer model as compared to the saline only controls. MT protein expression showed a 60%, 64%<br />and 78% immunopositivity in the co-treated groups respectively.The mean MT content in the precancer and the cancer<br />model was restored to near normal levels in all the three co-treated groups. Conclusion: These results suggest that<br />co-administration of aspirin, vitamin C or zinc resulted in a significant increase in MT mRNA gene expression, MT<br />protein expression and MT protein content which could possibly be one of the reasons for a chemo protective effect<br />against progression to colonic cancer in a chemically induced DMH model in rat.Zinc supplement had a greater effect<br />on metallothionein expression than aspirin or vitamin C.