Suppression of early stages of neoplastic transformation in a two-stage chemical hepatocarcinogenesis model: supplementation of vanadium, a dietary micronutrient, limits cell proliferation and inhibits the formations of 8-hydroxy-2'-deoxyguanosines and DNA strand-breaks in the liver of sprague-dawley rats.
Previous studies from our laboratory have demonstrated the potential anticarcinogenicity of vanadium, a dietary micronutrient in rat liver, colon, and mammary carcinogenesis models in vivo. In this paper, we have investigated further the antihepatocarcinogenic role of this essential trace element by studying several biomarkers of chemical carcinogenesis with special reference to cell proliferation and oxidative DNA damage. Hepatocarcinogenesis was induced in male Sprague-Dawley rats by chronic feeding of 2-acetylaminofluorene (2-AAF) at a dose of 0.05% in basal diet daily for 5 days a week. Vanadium in the form of ammonium metavanadate (0.5 ppm equivalent to 4.27 micromol/l) was supplemented ad lib to the rats. Continuous vanadium administration reduced relative liver weight, nodular incidence (79.99%), total number and multiplicity (P < 0.001; 68.17%) along with improvement in hepatocellular architecture when compared to carcinogen control. Vanadium treatment further restored hepatic uridine diphosphate (UDP)-glucuronosyl transferase and UDP-glucose dehydrogenase activities, inhibited lipid peroxidation, and prevented the development of glycogen-storage preneoplastic foci (P < 0.01; 63.29%) in an initiation-promotion model. Long-term vanadium treatment also reduced BrdU-labelling index (P < 0.02) and inhibited cell proliferation during hepatocellular preneoplasia. Finally, short-term vanadium exposure abated the formations of 8-hydroxy-2'-deoxyguanosines (P < 0.001; 56.27%), length:width of DNA mass (P < 0.01), and the mean frequency of tailed DNA (P < 0.001) in preneoplastic rat liver. The study indicates the potential role of vanadium in suppressing cell proliferation and in preventing early DNA damage in vivo. Vanadium is chemopreventive against the early stages of 2-AAF-induced hepatocarcinogenesis in rats.
Chakraborty
Tridib
T
Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, Calcutta 700032, West-Bengal, India.
Chatterjee
Amrita
A
Rana
Ajay
A
Rana
Basabi
B
Palanisamy
Ashokumar
A
Madhappan
Rajkumar
R
Chatterjee
Malay
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D014408:Biomarkers, Tumor; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014131:Trace Elements / Q000494:pharmacology; D014639:Vanadium / Q000494:pharmacology*
D014408:Biomarkers, Tumor; D002273:Carcinogens; D014131:Trace Elements; D014639:Vanadium; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine