title: Apoptosis and cell proliferation in rat hepatocytes induced by barbiturates.
abstract: To examine the effect on cell population in hepatocytes of phenobarbital (PB) and other barbiturates, PB, allobarbital (ALB), barbital sodium (BS) and barbituric acid (BA) were given orally to male rats for 7 consecutive days. Although there was no apparent change in non-promoting BA, hepatomegaly was induced by PB, BS and ALB, which are promoters of hepatocarcinogenesis. In PB- and BS-treated livers, hepatomegaly was attributable to hepatocyte proliferation and enzyme induction. In ALB-treated liver, it was attributable to enzyme induction. The level of cell proliferation was reduced to less than the control values following withdrawal of PB, ALB and BS. It seemed that the degree of suppression of cell proliferation following withdrawal of these compounds correlated to the degree of cell proliferation (PB>BS>ALB) during treatment. In PB-treated liver, apoptosis was induced during treatment, serving to eliminate the excess of hepatocytes. This suggests that short-term administration of PB neither induced suppression of apoptosis nor disturbed homeostasis of hepatocyte populations.
authors.affiliation: Shiraoka Research Station of Biological Science, Nissan Chemical Industries, Ltd., Saitama, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Furukawa
authors.forename: K
authors.initials: K
authors.lastname: Usuda
authors.forename: Y
authors.initials: Y
authors.lastname: Fujieda
authors.forename: T
authors.initials: T
authors.lastname: Tamura
authors.forename: Y
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: S
authors.initials: S
authors.lastname: Ikeyama
authors.forename: M
authors.initials: M
authors.lastname: Goryo
authors.forename: K
authors.initials: K
authors.lastname: Okada
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001462:Barbital / Q000009:adverse effects; D001463:Barbiturates / Q000009:adverse effects*; D001835:Body Weight; D001973:Bromodeoxyuridine / Q000737:chemistry; D002455:Cell Division / Q000187:drug effects; D006529:Hepatomegaly / Q000662:veterinary; D006993:Hypnotics and Sedatives / Q000009:adverse effects; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling / Q000662:veterinary; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008111:Liver Function Tests / Q000662:veterinary; D008113:Liver Neoplasms / Q000209:etiology / Q000473:pathology / Q000662:veterinary*; D008297:Male; D010634:Phenobarbital / Q000009:adverse effects; D051381:Rats; D011916:Rats, Inbred F344; D013047:Specific Pathogen-Free Organisms
chemical_list: D001463:Barbiturates; D006993:Hypnotics and Sedatives; D001462:Barbital; C084828:allobarbital; D001973:Bromodeoxyuridine; C032232:barbituric acid; D010634:Phenobarbital