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

Shinobu Sakamoto, Hidematsu Hirai, Hiroko Taga, Toshiyuki Uchikoshi, Tatsuya Sunaga, Yasuo Endo, Katsuhiko Kuwa, Hideki Kudo, Yasuyuki Kawachi, Noriyuki Kasahara, Ryohei Okamoto

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8 Scopus citations

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 α-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 AFIP 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 hepatocarcinogenesis.

Original languageEnglish (US)
Pages (from-to)145-150
Number of pages6
JournalCarcinogenesis
Volume11
Issue number1
DOIs
StatePublished - Jan 1990

ASJC Scopus subject areas

  • Cancer Research

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    Sakamoto, S., Hirai, H., Taga, H., Uchikoshi, T., Sunaga, T., Endo, Y., Kuwa, K., Kudo, H., Kawachi, Y., Kasahara, N., & Okamoto, R. (1990). Thymidine kinase and α-fetoprotein as biochemical markers of hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene treatment in rats. Carcinogenesis, 11(1), 145-150. https://doi.org/10.1093/carcin/11.1.145