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: Alda R D Sampaio, Carlos E A Chagas, Thomas P Ong, Fernando S Moreno
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 45 Issue 4 Pg. 563-7 (Apr 2007) ISSN: 0278-6915 [Print] England
• PMID: 17113696 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• beta Carotene
• Vitamin A
• gamma-Glutamyltransferase
• 1,2-Dimethylhydrazine
• Azacitidine

Topics

• 1,2-Dimethylhydrazine (toxicity)
• Animals
• Anticarcinogenic Agents (therapeutic use)
• Azacitidine (toxicity)
• DNA Repair
• Liver Neoplasms, Experimental (chemically induced, prevention & control)
• Male
• Rats
• Rats, Wistar
• Vitamin A (therapeutic use)
• beta Carotene (therapeutic use)
• gamma-Glutamyltransferase (analysis)