title: Vitamin A and beta-carotene inhibitory effect during 1,2-dimethylhydrazine induced hepatocarcinogenesis potentiated by 5-azacytidine.
abstract: 5-Azacytidine is being used for reactivation of tumor suppressor genes. However, its administration during DNA repair pontentiates hepatocarcinogenesis. We observed chemopreventive activities by vitamin A and beta-carotene during early hepatocarcinogenesis. Thus, in the present study we evaluated vitamin A and beta-carotene chemopreventive potential during early hepatocarcinogenesis potentiated by 5-azacytidine. Wistar rats received vitamin A (VAA group), beta-carotene (betaCA group) or corn oil (CO and COA groups). After three weeks of treatment, all animals were initiated with 1,2-dimethylhydrazine. Twelve hours later VAA, betaCA and COA groups received a single dose of 5-Azc. Hepatocytes were selected/promoted by 2-acetylaminofluorene and 70% partial hepatectomy. All animals were sacrificed six weeks after initiation. Compared to CO group (without 5-azacytidine), COA group presented higher (p<0.05) nodule multiplicity, larger (p<0.05) gamma-GT positive lesions that occupied a larger (p<0.05) area of liver section. Compared to COA group, VAA group presented decreased (p<0.05) nodule multiplicity while betaCA group tended to present smaller gamma-GT positive lesions and to decrease occupied liver section. These results reinforce vitamin A and beta-carotene chemopreventive potential. Considering that 5-azacytidine potentiates hepatocarcinogenesis, more studies are needed to elucidate the efficacy and safety of this drug for cancer control.
authors.affiliation: Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Alda R D
authors.initials: AR
authors.lastname: Sampaio
authors.forename: Carlos E A
authors.initials: CE
authors.lastname: Chagas
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Ong
authors.forename: Fernando S
authors.initials: FS
authors.lastname: Moreno
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001374:Azacitidine / Q000633:toxicity*; D004260:DNA Repair; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014801:Vitamin A / Q000627:therapeutic use*; D019207:beta Carotene / Q000627:therapeutic use*; D005723:gamma-Glutamyltransferase / Q000032:analysis
chemical_list: D016588:Anticarcinogenic Agents; D019207:beta Carotene; D014801:Vitamin A; D005723:gamma-Glutamyltransferase; D019813:1,2-Dimethylhydrazine; D001374:Azacitidine