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.

Effect of vitamin D3 on carcinogen-modified liver enzymes and tumour incidence in experimental rat mammary carcinogenesis.

The anticarcinogenic effect of vitamin D3 in relation to biochemical and morphological markers in 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced mammary carcinogenesis was investigated in two different sets of experiments. For each set, female Sprague-Dawley rats were divided into four groups, to allow comparison among treated and non-treated groups. At 50 days of age, animals of group B and C were given DMBA injection (0.5 mg/100 g body weight) through the tail vein, and normal control (group A) animals received the oil emulsion vehicle alone. Vitamin D3 at the dose of 0.3 microgram/0.1 ml propylene glycol was given orally twice a week, in carcinogen as well as non-carcinogen treated animals (group C and c), until the termination of the experiments (22-24 weeks for biochemical markers, and 35 weeks for morphology). At approximately 22-24 weeks, when marked lobular hyperplasia in DMBA control groups were confirmed through histology, the biochemical markers were modulated towards normal value for vitamin D3 in the treatment group, in comparison to the disturbed values caused by carcinogen administration in group B animals. Again, vitamin D3 supplementation was effective in reducing the tumour incidence (70% in comparison to 90% in group B). The results thus clearly concluded the antineoplastic potential of vitamin D3, and the existing correlation between biological and biochemical markers.