title: Impairment of lipoglycoprotein metabolism in rat liver cells induced by 1,2-dichloroethane.
abstract: BACKGROUND
  1,2-Dichloroethane (DCE) is a volatile liquid readily absorbed through dermal, digestive, or inhalatory routes. After inhalation or oral administration to rats, death occurs within a narrow range of concentrations (six hour LC50 = 5100 mg/m3). Exposure to single high doses of DCE resulted in adverse effects on the central nervous system, liver, kidneys, adrenals, and lungs. The liver showed fatty changes and hepatocellular necrosis with haemorrhage. These injuries are probably related to changes in several cell functions and constituents. Therefore, it was decided to investigate whether DCE was capable of impairing the secretion of hepatocellular lipoglycoproteins acting both at the level of the Golgi apparatus and endoplasmic reticulum.
  
  
  METHODS
  Isolated hepatocytes of Wistar rats were prelabelled with two precursors of lipoglycoproteins 3H-Na-palmitate and 14C-glucosamine, and then exposed to concentrations of DCE from mean (SD) 4.4 (0.03) to 6.5 (0.02) mM for different durations ranging from five to 60 minutes. To measure lipid and sugar bound radioactivity, a preliminary separation of cell homogenate, cytosol, total microsomes, Golgi apparatus, and lipoglycoproteins secreted into cell suspension medium was carried out.
  
  
  RESULTS
  After five minutes of exposure, DCE did not induce obvious changes in cell viability or lactic dehydrogenase leakage, but a significant (p < 0.01) depletion of reduced glutathione content was seen (40.10 (4.3) nM/10(6) cells). Furthermore, the cells poisoned by DCE started to show noticeable accumulation of 3H-Na-palmitate in the Golgi apparatus after five minutes (5103 (223) dpm/10(6) cells) and in the microsomes after 15 minutes (85,470 (7190) dpm/10(6) cells). There was a simultaneous significant increase in 14C-glucosamine content in the Golgi apparatus (690 (55) dpm/10(6) cells) and the microsomes (15,975 (2035) dpm/10(6) cells). The specific radioactivity of lipid and sugar moieties incorporated in secreted lipoglycoproteins was already significantly reduced after only five minutes of exposure (480 (57) dpm/10(6) cells for lipids, and 315 (45) dpm/10(6) cells for sugars).
  
  
  CONCLUSIONS
  Overall, DCE, like other haloalkanes, produces a block of secretion of hepatocellular lipoglycoproteins as early as five minutes after poisoning. The simultaneous percentage increases into Golgi apparatus and microsomes of lipid and sugar bound radioactivity suggest that lipid retention at the sites of processing of lipoglycoproteins would probably play an important part in the early stages of cellular accumulation of fat after exposure to DCE.
authors.affiliation: Division of Occupational Medicine, Ospedale S Martino, Genoa, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Cottalasso
authors.forename: G
authors.initials: G
authors.lastname: Barisione
authors.forename: L
authors.initials: L
authors.lastname: Fontana
authors.forename: C
authors.initials: C
authors.lastname: Domenicotti
authors.forename: M A
authors.initials: MA
authors.lastname: Pronzato
authors.forename: G
authors.initials: G
authors.lastname: Nanni
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005025:Ethylene Dichlorides / Q000378:metabolism / Q000506:poisoning*; D005944:Glucosamine / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005025:Ethylene Dichlorides; D006023:Glycoproteins; D010169:Palmitic Acids; D019308:Palmitic Acid; C024565:ethylene dichloride; D005978:Glutathione; D005944:Glucosamine