Regulatory Role of Zinc on the Biokinetics and Biodistribution of ⁶⁵Zn During the Initiation of Experimentally Induced Colon Cancer

Abstract

The present study was conducted to evaluate the kinetics of zinc utilization during the formation of colon carcinoma in an animal model of colon carcinogenesis. The rats were segregated into 4 groups: untreated control, 1,2 dimethylhydrazine (DMH) treated, zinc treated, and DMH+zinc treated. Colon carcinogenesis was initiated through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 wk. Zinc (in the form of zinc sulphate) was supplemented at a dose level of 227mg/L in drinking water, ad libitum for the entire duration of study. Whole body ⁶⁵Zn kinetics followed two-compartment kinetics, with Tb₁ representing the initial fast component of the biological half-life and Tb₂, the slower component. The Tb₁ component showed a significant elevation while the Tb₂ component was significantly diminished in DMH-treated rats, which, however, got normalized following zinc supplementation. The biodistribution and subcellular distribution of ⁶⁵Zn was significantly affected in DMH-treated rats when compared to normal control rats. However, zinc significantly reversed the altered ⁶⁵Zn uptake in different organs and various fractions of colon. The present study for the first time demonstrated a faster mobilization of zinc during initiation of experimentally induced colon carcinoma and provides a physiological basis for the role of zinc in colon tumorigenesis.

ACKNOWLEDGMENTS

This work was supported by a financial grant from the Indian Council of Medical Research (ICMR), New Delhi, India. There is no conflict of interest with regard to financial, personal, or other relationships with other people or organizations that could influence the present work.

Notes

^a P < 0.01 by Newman-Keuls test when values are compared with control group.

^b P < 0.05.

^c P < 0.01 by Newman-Keuls test when values of Group IV are compared with Group II.

^a P < 0.001 by Newman-Keuls test when values are compared with control group.

^b P < 0.05 by Newman-Keuls test when values of Group IV are compared with Group II.

^a P < 0.05.

^b P < 0.01.

^c P < 0.001 by Newman-Keuls test when values are compared with control group.

^d P < 0.05.

^e P < 0.01 by Newman-Keuls test when values of Group IV are compared with Group II.

^f P < 0.001 by Newman-Keuls test when values of Group IV are compared with Group II.

^a P < 0.01.

^b P < 0.001 by Newman-Keuls test when values are compared with control group.

^c P < 0.01.

^d P < 0.001 by Newman-Keuls test when values of Group IV are compared with Group II.