Vanadium inhibits DNA-protein cross-links and ameliorates surface level changes of aberrant crypt foci during 1,2-dimethylhydrazine induced rat colon carcinogenesis.

The trace mineral vanadium inhibits cancer development in a variety of experimental animal models. The present study was to gain insight into a putative anticancer effect of vanadium in a rat model of colon carcinogenesis. The in vivo study was intended to clarify the effect of vanadium on DNA-protein cross-links (DPC), surface level changes of aberrant crypt foci (ACF) and biotransformation status during 1,2-dimethylhydrazine (1,2-DMH) induced preneoplastic rat colon carcinogenesis. The comet assay showed statistically higher mean base values of DNA-protein mass (p<0.01) and mean frequencies of tailed cells (p<0.001) in the carcinogen-induced group after treatment with proteinase K. Treatment with vanadium in the form of ammonium monovanadate supplemented ad libitum in drinking water for the entire experimental period caused a significant (p<0.02) reduction (40%) in DNA-protein cross-links in colon cells. Further, the biotransformation status of vanadium was ascertained measuring the drug metabolising enzymes, glutathione S-transferase (GST) and cytochrome P-450 (Cyt P-450). Significantly, there was an increase in glutathione S-transferase and cytochrome P-450 levels (p<0.01 and p<0.02, respectively) in rats supplemented with vanadium as compared to their carcinogen controls. As an endpoint marker, we also evaluated the effect of vanadium on surface level changes of aberrant crypt foci induced by 1,2-DMH by scanning electron microscopy. Animals induced with 1,2-DMH and supplemented with vanadium showed a marked improvement in colonic architecture with less number of aberrant crypt foci in contrast to the animals induced with 1,2-DMH alone, thereby exhibiting its anti-carcinogenicity by modulating the markers studied herein.

Chemopreventive effects of vanadium toward 1,2-dimethylhydrazine-induced genotoxicity and preneoplastic lesions in rat colon.

In the present study, we have evaluated the antitumor effects of vanadium by monitoring DNA damage and chromosomal aberrations (CAs) during the early preneoplastic stage of 1,2-dimethylhydrazine (1,2-DMH)-induced colon cancer in male rats. Treatment with 20 mg/kg 1,2-DMH for 6 weeks resulted in the formation of aberrant crypt foci (ACF), a putative preneoplastic lesion associated with colon cancer development, while cotreatment with ammonium monovanadate (0.5 ppm in the drinking water) reduced ACF formation by 50% (P < 0.001). The 6-week treatment with 1,2-DMH also resulted in significantly higher levels of DNA damage in rat colon as measured by the Comet assay (higher mean values for length-to-width ratios (L:W) of DNA mass (P < 0.01) and mean frequencies of cells with comets (P < 0.001)). The vanadium cotreatment reduced DNA damage in colon cells by 32% (P < 0.02 and P < 0.001 for L:W and tailed cells, respectively). 1,2-DMH treatment also produced a 10-fold increase in the frequency of CAs in rat colon (P < 0.001), while cotreatment with vanadium resulted in a reduction in CAs after 2, 4, and 6 weeks of 1,2-DMH exposure (P < 0.01). Analysis of antioxidant defense enzyme activity in colonic mucosa indicated that glutathione reductase and catalase activities were increased in 1,2-DMH-treated rats; cotreatment with vanadium reduced these activities when compared to the carcinogen control (P < 0.001 and P < 0.02). These results demonstrate that the early protective effect of vanadium in chemically induced rat colon carcinogenesis may be mediated by a reduction of carcinogen-induced DNA damage.

Combined supplementation of vanadium and beta-carotene suppresses placental glutathione S-transferase-positive foci and enhances antioxidant functions during the inhibition of diethylnitrosamine-induced rat liver carcinogenesis.

BACKGROUND AND AIM: The present study was designed to investigate the chemopreventive effects of combined vanadium (V; 0.5 p.p.m.) and beta-carotene (BC; 120 mg/kg of basal diet) on diethylnitrosoamine (DEN)-induced and phenobarbital (PB)-promoted rat hepatocarcinogenesis. METHODS: All rats were subjected to two-thirds partial hepatectomy (PH) at the fourth week. After PH they were administered either trioctanoin alone (groups A', B', C' and D') or a single injection of DEN in trioctanoin at a dose of 10 mg/kg of body weight (groups A, B, C and D). Two weeks after the DEN treatment PB was administered (0.05% in basal diet) to all the DEN-treated rats and continued until the end of the experiment. Supplementation of V (groups B and B'), BC (groups C and C') or both V and BC (groups D and D') at the doses stated previously were started 4 weeks before DEN administration (at week 0) and continued until the 16th week. RESULTS: It was observed that in the DEN-treated and PB-promoted group (group A) the expression of the numbers and areas of the placental form of glutathione S-transferase (GST-P)-positive altered hepatic foci (AHF) was maximum. Treatment with V (group B) and BC (group C) significantly reduced the expression of GST-P-positive AHF by 29.5% and 42.8%, respectively. An additive protection action (65.7%) was noticed in group D, which received both V and BC for the entire period of the experiment. It was also observed that supplementation of V and BC for the entire period of the experiment significantly reduced the number and size of the hyperplastic nodules, while the combination treatment worked as an additive effect, reducing the number and size of the hyperplastic nodules to 22% from 89%. Moreover, a significantly reduced level of cytosolic glutathione (P < 0.001) and glutathione-S-transferase (P < 0.001) activity and stabilization of aerobic metabolism and hepatic architecture of the cells as compared with carcinogen control were observed in the V + BC-treated group. CONCLUSION: The present study suggests that V, an essential trace element, may be useful in combination with BC, an antioxidant, in the inhibition of experimentally induced rat hepatocarcinogenesis.

Effect of vanadium on colonic aberrant crypt foci induced in rats by 1,2 dimethyl hydrazine.

AIM: To investigate the chemo preventive effects of vanadium on rat colorectal carcinogenesis induced by 1,2-dimethylhydrazine (DMH). METHODS: Male Sprague-Dawley Rats were randomly divided into four groups. Rats in Group A received saline vehicle alone for 16 weeks. Rats in Group B were given DMH injection once a week intraperitoneally for 16 weeks; rats in Group C, with the same DMH treatment as in the Group B, but received 0.5-ppm vanadium in the form ammonium monovanadate ad libitum in drinking water. Rats in the Group D received vanadium alone as in the Group C without DMH injection. RESULTS: Aberrant crypt foci (ACF) were formed in animals in DMH-treated groups at the end of week 16. Compared to DMH group, vanadium treated group had less ACF (P<0.001). At the end of week 32, all rats in DMH group developed large intestinal tumors. Rats treated with vanadium contained significantly few colonic adenomas and carcinomas (P<0.05) compared to rats administered DMH only. In addition, a significant reduction (P<0.05) in colon tumor burden (sum of tumor sizes per animal) was also evident in animals of Group C when compared to those in rats of carcinogen control Group B. The results also showed that vanadium significantly lowered PCNA index in ACF (P<0.005). Furthermore, vanadium supplementation also elevated liver GST and Cyt P-450 activities (P<0.001 and P<0.02, respectively). CONCLUSION: Vanadium in the form of ammonium monovanadate supplemented in drinking water ad libitum has been found to be highly effective in reducing tumor incidence and preneoplastic foci on DMH-induced colorectal carcinogenesis. These findings suggest that vanadium administration can suppress colon carcinogenesis in rats.

Vanadium inhibits placental glutathione S-transferase (GST-P) positive foci in 1,2-dimethyl hydrazine induced rat colon carcinogenesis.

Vanadium (V) has recently been found to possess potent anti-neoplastic activity in rat colon carcinogenesis. In the present study attempts have been made to investigate the expression of the number and area of aberrant crypt foci positive for placental glutathione S-transferase (GST-P) during 1,2-dimethyl hydrazine (DMH)-induced rat colon carcinogenesis. Male Sprague Dawley rats were randomly divided into four groups. Rats in group A were designed as normal controls. Group B animals received DMH once a week (20 mg/kg body wt.) intraperitoneally for 16 weeks. Group C rats received the same treatment of DMH as in group B, along with 0.5-ppm vanadium as ammonium monovanadate ad libitum in drinking water throughout the experiment. Vanadium alone was given to Group D rats without any DMH injection. The expression of the number and the area of aberrant crypt foci (ACF) positive for GST-P was maximum in DMH-treated group. Vanadium-treated rats significantly reduced (P < 0.001) the expression of GST-P positive ACF cells (by 71.13%) for the entire period of the study. Moreover the histopathological examination also showed that vanadium action could minimize the aberrant crypt foci (P < 0.001). Furthermore, vanadium supplementation also elevated SOD activities in both liver and colon (P < 0.01, P < 0.02 and P < 0.01, P < 0.02 respectively) when compared to their carcinogen counterparts. Our results confirm that vanadium is particularly effective in limiting the action of the carcinogen, thereby establishing its anticarcinogenicity in chemically induced rat colon carcinogenesis.