Intraperitoneal injection of D-galactosamine provides a potent cell proliferation stimulus for the detection of initiation activities of chemicals in rat liver

Yoshiji Asaoka, Hiroki Sakai, Naofumi Takahashi, Akihiro Hirata, Tetsuya Tsukamoto, Masami Yamamoto, Tokuma Yanai, Toshiaki Masegi, Masae Tatematsu

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4 Citations (Scopus)

Abstract

In an in vivo 5-week initiation assay model, chemical hepatectomy by hepatotoxicant administration was utilized as a cell proliferation stimulus as an alternative to the two-thirds partial hepatectomy. The study investigated the effect of an intraperitoneal (i.p.) injection of D-galactosamine (D-gal) for this purpose in a medium-term liver bioassay, with a further focus on cell proliferation kinetics and cytochrome P450 (CYP) expression. In experiment I, cell proliferation in rat liver after a single administration of D-gal (700 mg kg-1, i.p.) was analysed by the bromodeoxyuridine (BrdU) labeling method, and CYP isozymes were quantified by immunoblotting. In experiment II, the induction of glutathione S-transferase placental form (GST-P) positive foci by 1,2-dimethylhydrazine (DMH) was evaluated in a modified in vivo 5-week initiation assay model. At 84 hours after single administration of D-gal (i.p.) the BrdU index was markedly elevated (27.5% ± 9.5%). Although CYP 2E1 and 1A2 apoprotein contents decreased transiently to less than 20% of the control level, subsequently they recovered to 60% and 40% of the control level, respectively, at 84 hours. Induction of GST-P positive foci in the group given DMH at 84 hours after a single administration of D-gal was significantly greater than in the control group, correlating with the kinetics of cell proliferation. In conclusion, the sensitivity of the present initiation assay using D-gal i.p. is high, so that D-gal i.p. can be considered an effective cell proliferation stimulus.

Original languageEnglish
Pages (from-to)554-561
Number of pages8
JournalJournal of Applied Toxicology
Volume25
Issue number6
DOIs
Publication statusPublished - 01-11-2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Toxicology

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