Inhibition of hepatocellular carcinoma development and erythrocyte polyamine levels in ODS rats fed on 3'-methyl-4-dimethylaminoazobenzene by hemicalcium ascorbate, 2-O-octadecylascorbic acid, and ascorbyl palmitate

• Published in: Cancer detection and prevention Vol. 20; no. 2; p. 137
• Main Authors: Shimpo, K, Takahashi, H, Tsuda, H, Hibino, T, Kawai, K, Kimura, C, Nagatsu, T, Fujita, K
• Format: Journal Article
• Language: English
• Published: England 1996
• Subjects: Animals; Antimutagenic Agents - chemistry; Antimutagenic Agents - pharmacology; Ascorbic Acid - analogs & derivatives; Ascorbic Acid - chemistry; Ascorbic Acid - pharmacology; Body Weight - drug effects; Carcinogens; Erythrocytes - chemistry; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; Liver - drug effects; Liver - pathology; Liver Neoplasms, Experimental - blood; Liver Neoplasms, Experimental - chemically induced; Liver Neoplasms, Experimental - pathology; Liver Neoplasms, Experimental - prevention & control; Male; Methyldimethylaminoazobenzene; Organ Size - drug effects; Putrescine - analysis; Rats; Spermidine - analysis; Spermine - analysis
• ISSN: 0361-090X; 1873-443X

We examined the modifying effect of hemicalcium ascorbate (Ca-Asc), and its lipophilic derivatives, 2-O-octadecylascorbic acid (CV-3611) and ascorbyl palmitate (AscP), on hepatocarcinogenesis by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) in ODS rats (a mutant unable to synthesize ascorbic acid). Male 14-week-old ODS rats were given a modified AIN-A diet or the diet containing 0.06% 3'-Me-DAB, and drinking water containing 0.1% ascorbic acid. Rats were divided into the following eight groups: Group 1, no treatment (basal diet alone); Group 2, Ca-Asc; Group 3, CV-3611; Group 4, AscP;Group 5, 3'-Me-DAB; Group 6, 3'-Me-DAB + Ca-Asc; Group 7, 3'-Me-DAB + CV-3611; and Group 8, 3'-Me-DAB + AscP. Ca-Asc (2 g/kg), CV-3611 (0.2 g/kg), and AscP (0.6 g/kg) was administered once every day by gavage. 3'-Me-DAB was given in the basal diet. After 17 weeks, animals were killed by exsanguination, and the liver was weighed and processed for histological examination. Treatment by CV-3611 exerted a marked inhibitory effect on the development of 3'-Me-DAB-induced hepatocellular carcinomas (HCC) as measured by multiplicity. Although less effective than CV-3611, Ca-Asc and AscP also showed inhibitory effect. We have also studied the correlation of erythrocyte (RBC) polyamine levels and HCC development. RBC polyamine levels were inhibited by Ca-Asc and its derivatives, indicating it may be a marker of hepatocarcinogenesis.