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.
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.
Shimpo
K
K
Institute for Comprehensive Medical Science, School of Medicine, Fujita Health University, Aichi, Japan.
Takahashi
H
H
Tsuda
H
H
Hibino
T
T
Kawai
K
K
Kimura
C
C
Nagatsu
T
T
Fujita
K
K
D000818:Animals; D016587:Antimutagenic Agents / Q000737:chemistry / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D004912:Erythrocytes / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008749:Methyldimethylaminoazobenzene; D009929:Organ Size / Q000187:drug effects; D011700:Putrescine / Q000032:analysis; D051381:Rats; D013095:Spermidine / Q000032:analysis; D013096:Spermine / Q000032:analysis
D016587:Antimutagenic Agents; D002273:Carcinogens; D016166:Free Radical Scavengers; D013096:Spermine; D008749:Methyldimethylaminoazobenzene; C061185:2-O-octadecylascorbic acid; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid; D013095:Spermidine; D011700:Putrescine