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.
Kanna
P Suresh
PS
Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, P.B. No. 17028, Kolkata (Calcutta)-700032, India.
Saralaya
M G
MG
Samanta
K
K
Chatterjee
M
M
D019813:1,2-Dimethylhydrazine; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D020552:Comet Assay; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D005982:Glutathione Transferase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008855:Microscopy, Electron, Scanning; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014639:Vanadium / Q000494:pharmacology*
D011506:Proteins; D014639:Vanadium; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; D019813:1,2-Dimethylhydrazine