Application of radiotracers in the assessment of prophylactic role of zinc in experimental model of colon carcinogenesis

Full text: The present study elucidated the modulatory effects of zinc in 1,2 dimethylhydrazine (DMH) induced colon carcinogenesis using radiotracer techniques. Rats were segregated into four groups viz., untreated control, DMH treated, zinc treated, DMH+zinc treated. Colon carcinogenesis was induced through weekly subcutaneous injections of DMH (30 mg/Kg body weight) for 16 weeks. Zinc was supplemented to rats at a dose level of 227mg/L in drinking water, ad libitum. The prophylactic role of zinc was assessed by following radiotracer techniques viz: whole body biological half life of 65 Zn and 65 Zn biodistribution, subcellular distribution, uptake of 3H-Thymidine to assess rate of DNA synthesis, radiorespirometric determination of 14C-D-Glucose metabolism and in-vitro uptake of labeled aminoacids. The statistical significance of the data has been determined by using one way analysis of variance (ANOVA) followed by multiple post - hoc test. The carcinogenic state in the animals was confirmed by histopathological examination, whereby, well-differentiated signs of dysplasia were evident in colonic tissue sections of DMH treated rats. The biokinetics study of zinc revealed a significant decrease in the biological half life of 65 Zn. Also, DMH treatment caused a significant increase in the percent uptake values of 65 Zn in the colon, small intestine, kidney and blood, whereas a significant decrease was observed in the liver. The uptake rates of amino acids viz: 14C-glycine, 14C-alanine and 14C-lysine were significantly higher in the DMH treated colons. Moreover, a significant increase in the uptake and turnover of 14C-D-Glucose was also observed after DMH treatment. A significant increase in the (3H)-thymidine uptake was observed following 16 weeks DMH treatment. However, supplementation of zinc significantly reversed the proliferative effect of DMH as evidenced by ameliorating the altered parameters. Radiotracer techniques play an important role in assessing positive beneficial effect of zinc against chemically induced colonic preneoplastic progression