Previous studies have shown that dietary
micronutrient vanadium can protect neoplastic development induced by chemical
carcinogens. Current investigation is an attempt to evaluate the role of
vanadium (4.27 micro mol/l) in inhibiting 1,2 dimethyhydrazine (
DMH) (20 mg/kg
body weight) induced rat colon
carcinogenesis. We investigated the effect of
vanadium against the formation of
DMH-induced
O(6)-methylguanine (O(6)-Meg)
DNA adduct, a potent cytotoxic and mutagenic agent for
colon cancer. Supplementation of
vanadium significantly reduced the hepatic (P<0.05), and colonic (at three sequential time points; ANOVA, F=4.96, P<0.05) O(6)-Meg
DNA adduct levels in rats, indicating
vanadium's potency in limiting the initiation event of colon
carcinogenesis. Removal of initiated and damaged precancerous cells by apoptosis can prevent
tumorigenesis and further
malignancy. DNA fragmentation study revealed the
vanadium-mediated apoptotic induction in colon
tumors. The increased value of apoptotic index (AI) (62.27%; P<0.01) in subsequent TUNEL assay further confirmed the apoptosis induction by
vanadium. This paralleled the nuclear immunoexpression of p53. A significant positive correlation between p53 immunoexpression and AI (P=0.0026, r=0.83, r(2)=0.69) links its association with
vanadium-mediated apoptotic induction.
Vanadium treatment also abated the
mRNA expression of iNOS (54.03%), reflecting its protective effect against
nitric oxide-mediated genotoxicity and colon
tumorigenesis. These studies cumulatively provide strong evidence for the inhibitory actions of
vanadium against
DMH-induced genotoxicity and
carcinogenesis in rat colon.