[Thymidine kinase activities in sera and liver tissues during hepatocarcinogenesis in rats treated with 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB)].
It is known that a high incidence of hepatocellular carcinoma in rat liver can be induced with 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). In the present study, we investigated serum levels of alpha-fetoprotein (AFP) and thymidine kinase (TK), DNA-synthesizing enzyme in the salvage pathway, and tissue TK and its isozyme activities in the liver of rats treated with 3'-MeDAB. Serum TK activities rose abruptly right after the onset of 3'-MeDAB treatment, peaking after one week and then gradually decreasing. At 3 weeks, though serum TK was decreasing, serum AFP and tissue TK began to increase, and oval cells appeared in the liver. At 5 weeks, though serum TK reached a nadir, serum AFP and tissue TK formed transient peaks, and oval cells occupied a major part of the hepatic lobules with hyperplastic nodules. Thereafter, serum TK continued to increase, and serum AFP and tissue TK, after transiently decreasing, re-increased; at 20 weeks, each value was at high level, and mixed type hepatocarcinoma was observed. The liver TK isozymes were separated into 3 types by DEAE-cellulose column chromatography. A 3'-MeDAB induced a remarkable increase in activity of cytosolic and fetal type isozyme in non-tumorous regions of livers at 5 weeks and tumorous regions at 20 weeks. These results indicate that biochemical changes in 3'-MeDAB-treated rat liver may provide a valuable insight into two step process in hepatocarcinogenesis.
Sakamoto
S
S
Tumor Laboratory, Tokyo Medical and Dental University.
Kuwa
K
K
Kawachi
Y
Y
Kudo
H
H
Kasahara
N
N
Kato
T
T
Okamoto
R
R
Taga
H
H
Hirai
H
H
Sunaga
T
T
D000818:Animals; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D008749:Methyldimethylaminoazobenzene; D051381:Rats; D013937:Thymidine Kinase / Q000097:blood / Q000378:metabolism*
D008749:Methyldimethylaminoazobenzene; D013937:Thymidine Kinase