Molecular basis of vanadium-mediated inhibition of hepatocellular preneoplasia during experimental hepatocarcinogenesis in rats
Chakraborty, T; Swamy, A; Chatterjee, A; Rana, B; Shyamsundar, A; Chatterjee, M
HERO ID
459018
Reference Type
Journal Article
Year
2007
Language
English
PMID
| HERO ID | 459018 |
|---|---|
| In Press | No |
| Year | 2007 |
| Title | Molecular basis of vanadium-mediated inhibition of hepatocellular preneoplasia during experimental hepatocarcinogenesis in rats |
| Authors | Chakraborty, T; Swamy, A; Chatterjee, A; Rana, B; Shyamsundar, A; Chatterjee, M |
| Journal | Journal of Cellular Biochemistry |
| Volume | 101 |
| Issue | 1 |
| Page Numbers | 244-258 |
| Abstract | Carcinogen-induced early DNA lesions and metallothionein (MT) over-expression have been implicated in cell proliferation and thereby subsequent expression of premalignant phenotype of the cell. We have therefore investigated the chemopreventive potential of vanadium in a multi-biomarker approach, viz. 8-hydroxy-2' -deoxyguanosines (8-OHdGs), DNA single-strand breaks (SSBs), DNA-protein crosslinks (DPCs), chromosomal aberrations (CAs), in situ MT expression, and cell proliferation in rat liver preneoplasia. Hepatocarcinogenesis was induced in male Sprague-Dawley rats with a single, necrogenic, intraperitoneal (i.p.) injection of diethylnitrosamine (DEN) (200 mg/Kg body weight) at week 4 of the experimental protocol followed by promotion with phenobarbital (PB) (0.05% in basal diet), on and from week 8 and continued till 32 weeks in a long-term regimen. There was a significant and steady elevation of modified DNA bases 8-OHdGs (P < 0.0001; 90.69%) along with substantial increments of the extent of SSBs (P < 0.001) and CAs (P < 0.001) following DEN exposure. Supplementation of vanadium at a dose of 0.5 ppm abated the formations of 8-OHdGs (80.63%; P < 0.0001), SS-DNAs (P < 0.001) and SSBs/DNA unit (P < 0.01; 56.39%), DPCs (59.26%; P < 0.0001) and CAs (71.52%; P < 0.001) in preneoplastic rat liver studied at various time points. Low dose of vanadium treatment further reduced liver-MT immunoreactivity (P < 0.05) and BrdU-labeling index (P < 0.02) and a significant positive correlation (r=0.92; r(2) =0.85; P=0.0001) was noted between them. Continuous vanadium administration also decreased nodular incidence (66.67%) and nodule multiplicity (62.12%; P < 0.001) along with substantial improvement in the altered hepatocellular phenotype when compared to DEN+PB treatment alone. The study indicates that vanadium-mediated suppression of cell proliferation and resulting premalignant expression might be due to the observed reductions in hepatic 8-OHdGs, SSBs, DPCs, CAs, and MT immunoreactivity. Vanadium is chemopreventive for DEN-induced hepatocellular preneoplasia in rats. |
| Doi | 10.1002/jcb.21169 |
| Pmid | 17243116 |
| Wosid | WOS:000245909200021 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |