title: 1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene induces substantial hyperplasia in fibrotic mouse liver.
abstract: The proliferative response of hepatocytes in vivo can be induced by two mechanisms: severe damage to hepatic tissue results in regenerative growth and so-called primary hepatocyte mitogens can initiate liver cell proliferation without preceding loss of parenchyma. The regulation of the two responses is quite different. The decreased regenerative response of cirrhotic/fibrotic liver is well known, and is a severe obstacle to surgery of the diseased liver. In the present experiments we investigated the efficiency of a primary hepatocyte mitogen 1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOB) on two different liver cirrhosis/fibrosis models in mice induced by chronic administration of CCl(4)  and thioacetamide respectively. BrdU incorporation and cyclin A expression established clearly that there is a reduced but still powerful mitogenic response of the fibrotic livers. Therefore, primary hepatocyte mitogens appear to be suitable to be used to rescue the regenerative response of cirrhotic livers.
authors.affiliation: First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: Edina
authors.initials: E
authors.lastname: Bugyik
authors.forename: Katalin
authors.initials: K
authors.lastname: Dezso
authors.forename: Eszter
authors.initials: E
authors.lastname: Turányi
authors.forename: Kinga
authors.initials: K
authors.lastname: Szurián
authors.forename: Sándor
authors.initials: S
authors.lastname: Paku
authors.forename: Peter
authors.initials: P
authors.lastname: Nagy
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects*; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006965:Hyperplasia; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011725:Pyridines / Q000494:pharmacology*; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D013853:Thioacetamide / Q000633:toxicity; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019925:Cyclin A; D011725:Pyridines; D016212:Transforming Growth Factor beta; D013853:Thioacetamide; C028474:1,4-bis(2-(3,5-dichloropyridyloxy))benzene; D002251:Carbon Tetrachloride; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C101679:Cyp2b10 protein, mouse; D000072467:Cytochrome P450 Family 2; D001973:Bromodeoxyuridine