title: Vanadium inhibits the development of 2-acetylaminofluorene-induced premalignant phenotype in a two-stage chemical rat hepatocarcinogenesis model.
abstract: In recent years, research on the biological influence of micronutrients in cancer has grown enormously. Among these, vanadium, a dietary micronutrient present in mammalian tissues has received considerable attention as a limiting agent. In the present study, attempts have been made to investigate the in vivo antitumour potentials of this micronutrient at the 0.5 ppm dosage in drinking water in a defined model of a two-stage experimental rat hepatocarcinogenesis. The chemopreventive effect of vanadium was assessed by studying certain biomarkers, such as development of gamma-glutamyltranspeptidase (GGT)-positive foci, levels of some essential trace elements, in situ expression of proliferating cell nuclear antigen (PCNA) and chromosomal aberrations. Hepatocarcinogenesis was induced in male Sprague-Dawley rats by chronic feeding of 2-acetylaminofluorene (0.05% in basal diet) on and from week 4. Vanadium administration throughout the experiment reduced the relative liver weight, nodular incidence (66.70%), total number and multiplicity (79.93%) and restored hepatic levels of selenium (Se) and iron (Fe) (P < 0.001) when compared to the carcinogen control. Moreover, long-term vanadium treatment significantly abated the expressions of GGT (P < 0.001) and PCNA with concomitant reduction in PCNA immunolabeling index (P < 0.001; 36.62%). Finally, the anticlastogenic potential of vanadium was reflected through its ability to inhibit early chromosomal aberrations (P < 0.001; 45.17%) in 2-AAF-challenged rat hepatocytes. Our results suggest that supplementary vanadium at a dose of 0.5 ppm, when administered continuously throughout the study, than administered either in the initiation or promotion phase alone, is very much effective in suppressing neoplastic transformation in vivo. We conclude the significant role of vanadium in limiting cell proliferation and chromosomal aberrations during the preneoplastic stages of hepatocarcinogenesis in rats.
authors.affiliation: Division of Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, PO Box 17028, Calcutta-700032, West Bengal, India.
authors.forename: Tridib
authors.initials: T
authors.lastname: Chakraborty
authors.forename: Amrita
authors.initials: A
authors.lastname: Chatterjee
authors.forename: M G
authors.initials: MG
authors.lastname: Saralaya
authors.forename: D
authors.initials: D
authors.lastname: Dhachinamoorthi
authors.forename: Malay
authors.initials: M
authors.lastname: Chatterjee
mesh_terms: D015073:2-Acetylaminofluorene / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D002869:Chromosome Aberrations / Q000139:chemically induced; D005982:Glutathione Transferase / Q000378:metabolism; D006498:Hepatectomy; D007150:Immunohistochemistry; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D008670:Metals / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000517:prevention & control*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013054:Spectrophotometry, Atomic; D014639:Vanadium / Q000494:pharmacology*; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D002273:Carcinogens; D008670:Metals; D018809:Proliferating Cell Nuclear Antigen; D014639:Vanadium; D015073:2-Acetylaminofluorene; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase