Preneoplastic liver cell foci expansion induced by thioacetamide toxicity in drug-primed mice

Preneoplastic liver cell foci expansion induced by thioacetamide toxicity in drug-primed mice
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DOI:
10.1016/j.yexmp.2006.02.006
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发表时间:
2006-08-01
影响因子:
3.6
通讯作者:
French, Samuel W.
French, Samuel W.
中科院分区:
医学3区
文献类型:
--
作者:
Roomi, M. Waheed;Gaal, Karl;French, Samuel W.

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Mice primed by feeding griseofulvin or diethyl 1,4-dihydro 1,4,6-trimethyl 3,5-pyridine decarboxylate for 5 months followed by drug withdrawal for I month (drug-primed mice) were given thioacetamide intraperitoneally, and the livers were subsequently studied at intervals up to 7 days. The hepatocellular proliferative response was measured by immunostaining for proliferative cell nuclear antigen. Necrosis was followed by measuring ALT. Mallory bodies were identified by immunoperoxidase stains for ubiquitin and cytokeratin. Preneoplastic foci were localized using immuno fluorescence stain for glutathione S-transferase (GST mu) and histochemical stain for gamma glutamyl transpeptidase (GGT). The results showed that the preneoplastic foci selectively proliferated and expanded and formed nodules as indicated by quantitation of nuclei stained positive for proliferating cell nuclear antigen after thioacetamide treatment. Data support the hypothesis that the preneoplastic foci consisted of clones of hepatocytes which preferentially express GST mu, GGT and Mallory bodies. These preneoplastic cells selectively proliferate in response to the promoter effects of necrosis-induced liver cell regeneration ("chemical partial hepatectomy"). (c) 2006 Elsevier Inc. All rights reserved.