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Intraperitoneal injection of d‐ galactosamine provides a potent cell proliferation stimulus for the detection of initiation activities of chemicals in rat liver
Author(s) -
Asaoka Yoshiji,
Sakai Hiroki,
Takahashi Naofumi,
Hirata Akihiro,
Tsukamoto Tetsuya,
Yamamoto Masami,
Yanai Tokuma,
Masegi Toshiaki,
Tatematsu Masae
Publication year - 2005
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1095
Subject(s) - in vivo , cell growth , intraperitoneal injection , bromodeoxyuridine , glutathione , chemistry , proliferating cell nuclear antigen , liver regeneration , cell , liver cell , medicine , endocrinology , pharmacology , microbiology and biotechnology , biochemistry , biology , enzyme , regeneration (biology)
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. Copyright © 2005 John Wiley & Sons, Ltd.