Tumor-specific action of sodium 5,6-benzylidene-L-ascorbate in N-nitrosodiethylamine-administered mouse model.
In order to elucidate the mechanisms of antitumor action of sodium 5,6-benzylidene-L-ascorbate (SBA), we established a mouse hepatocellular carcinoma model by oral administration of N-nitrosodiethylamine (NDA) and examined the ascorbate radical intensity and putrescine content in the liver. The oral intake of NDA induced precancerous lesion and a significant increase in putrescine content among three major polyamines. When the oral intake of NDA was stopped, morphological changes were reversed. ESR spectroscopy showed that the homogenate of precancerous tissues produced greater amounts of ascorbate radical than that of normal liver tissue. Intravenous administration of SBA 30 minutes before removal of the liver prolonged the higher level of ascorbate radical generation in the homogenate of precancerous tissue. The antitumor activity of SBA might be due to the long-term production of radicals in tumor tissues by its prooxidant action.
Asano
K
K
Department of Physiology, School of Medicine, Showa University, Tokyo, Japan.
Satoh
K
K
Kochi
M
M
Kusama
K
K
Sakagami
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001597:Benzylidene Compounds / Q000494:pharmacology*; D004052:Diethylnitrosamine; D004578:Electron Spin Resonance Spectroscopy; D007700:Kinetics; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D011073:Polyamines / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D000970:Antineoplastic Agents; D000975:Antioxidants; D001597:Benzylidene Compounds; D011073:Polyamines; D013481:Superoxides; D004052:Diethylnitrosamine; D001205:Ascorbic Acid; C070680:zilascorb