Thymidine kinase and alpha-fetoprotein as biochemical markers of hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene treatment in rats.
It is known that a high incidence of hepatocellular carcinoma in rat liver can be induced by such azo dye carcinogens as 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). Thymidine kinase (TK) catalyzes the formation of deoxythymidine monophosphate (dTMP) by the phosphorylation of thymidine via the salvage pathway. In the present study, we investigated serum alpha-fetoprotein (AFP) and TK levels, and tissue TK and its isozyme activities in the liver of rats treated with 3'-MeDAB. Serum TK activities rose abruptly directly after the onset of 3'-MeDAB treatment, peaking after 1 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 three types by DEAE-cellulose column chromatography. A 3'-MeDAB diet 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 early biochemical changes in 3'-MeDAB-induced hepatocarcinoma in rats may serve as a useful model and provide a valuable insight in hepatocarcinogensis.
Sakamoto
S
S
Medical Research Institute, Tokyo Medical and Dental University, Japan.
Hirai
H
H
Taga
H
H
Uchikoshi
T
T
Sunaga
T
T
Endo
Y
Y
Kuwa
K
K
Kudo
H
H
Kawachi
Y
Y
Kasahara
N
N
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D007527:Isoenzymes / Q000097:blood*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008749:Methyldimethylaminoazobenzene / Q000633:toxicity*; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013937:Thymidine Kinase / Q000097:blood*; D013997:Time Factors; D000509:alpha-Fetoproteins / Q000032:analysis*; D004124:p-Dimethylaminoazobenzene
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D000509:alpha-Fetoproteins; D008749:Methyldimethylaminoazobenzene; D004124:p-Dimethylaminoazobenzene; D013937:Thymidine Kinase