Thymidine kinase and α-fetoprotein as biochemical markers of hepatocarcinogenesis induced by 3′–methyl–4–dimethylaminoazobenzene treatment in rats

Abstract

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.

Liver Injury Models for Induction of Hepatic Oval Cells in Rodents

“…Nearly 100% of rats develop hepatocellular carcinoma after 20 weeks of 3'-Me-DAB diet [143]. Measuring serum AFP levels while on 3'-Me-DAB demonstrates two peaks: the first corresponds with the appearance of oval cells while the second indicates the development of hyperplastic nodules and hepatocellular carcinoma [143,144].…”

“…Depending on the injury agent, the first appearance of oval cells may be anytime between 1 day to 3 weeks after inducing the injury [51,62,80,143,181] while peak response varies between 5 days to 6 weeks [20,50,148,161]. Cessation of the injury agent leads to termination of oval cell response [182,183] although changes to the liver such as cholangiofibrosis are not reversed once formed [50].…”

Suppression of DMBA-Induced Mouse Skin Tumor Development by Inositol Hexaphosphate and Its Mode of Action

“…Skin (1 cm 2 ) was removed from the treated interscapular region and separated and epidermal extract was prepared according to the method described by Sakamoto et al (21). Skin (1 cm 2 ) was removed from the treated interscapular region and separated and epidermal extract was prepared according to the method described by Sakamoto et al (21).…”

Increase of DNA Synthesis in Uterine Adenomyosis in Mice with Ectopic Pituitary Isograft

“…High TS and TK activités have been observed in rapidly proliferating tissues such as target organs stimulated with some hormones [15,16]. fetal [9] and neoplastic [17,18] tissues. In the present study, we investigated the activities of TS and TK in uterine adenomyosis induced by EPI.…”