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.
Kanna
P Suresh
PS
Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
Mahendrakumar
C B
CB
Indira
B N
BN
Srivastawa
Sunil
S
Kalaiselvi
K
K
Elayaraja
T
T
Chatterjee
Malay
M
D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D003106:Colon / Q000187:drug effects*; D020552:Comet Assay; D004249:DNA Damage; D005980:Glutathione Reductase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014639:Vanadium / Q000494:pharmacology*
D009153:Mutagens; D014639:Vanadium; D002374:Catalase; D005980:Glutathione Reductase; D019813:1,2-Dimethylhydrazine