Adult Rat Hepatocytes in Primary Culture. VII. Proliferative and Functional Properties of Cells from Ethanol‐Intoxicated Animals: Evidence for a Reversible Albumin ‘Production Defect’

Pushkaraj J. Lad, W. Thomas Shier, Harold Skelly, Bernard de Hemptinne, Hyam L. Leffert

Research output: Contribution to journalArticle

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Abstract

Properties of long‐term cultures of hepatocytes isolated from nutritionally maintained adult rats treated in vivo for 8–12 days with ethanol to achieve blood levels of 200–220 mg ethanol/dl (experimental group) and from isocalorically maintained mock‐treated (control) rats were compared. Two kinds of treatment protocols were used: intragastric intubation or inhalation chambers. Similar results were observed with cultured cells obtained from either protocol. Hepatocytes in ‘monolayers’ from both animal groups showed unimpaired proliferative responses with respect to (a) cell multiplication and DNA synthesis rates during an asynchronous 12‐day growth cycle and (b) proliferogenic peptides [insulin, glucagon, and epidermal growth factor (EGF)] that reinitiate DNA synthesis parasynchronously during late stationary phase (days 12–13). Quantitative differences in [3H]leucine uptake into total proteins (cellular plus ‘secreted’) were not detected during the growth cycle. However, during stationary phase (days 8–12), 25%‐75% less [3H]leucine‐labeled albumin was released into culture fluids by hepatocytes from experimental livers than by hepatocytes from control livers. More pronounced differences were seen when albumin in the same culture fluids was measured by radioimmunoassay in contrast to measurements of [3H]leucine‐labeled albumin in these fluids. The defect was reversible since it was not seen in stationary‐phase hepatocyte cultures prepared from rats withdrawn more than 7 days from ethanol treatment whose blood alcohol levels had fallen to 0 mg ethanol/dl. These findings are consistent with the hypothesis that, with respect to albumin production by hepatocytes, chronic ethanol exposure induces a specific but reversible ‘defect’. Because this defect is not seen in short‐term hepatocyte cultures, long‐term cultures should facilitate attempts to understand the molecular and cellular causes of this functional impairment.

Original languageEnglish (US)
Pages (from-to)72-79
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Volume6
Issue number1
DOIs
StatePublished - Jan 1982

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