title: Interaction of hypoxia and carbon tetrachloride toxicity in hepatocyte monolayers.
abstract: The toxicity of carbon tetrachloride (CCl4) in monolayer cultures of primary hepatocytes was investigated at oxygen concentrations that prevail in the liver under conditions that range from normoxia to hypoxia: 0.5, 1, 2, and 20% O2. CCl4 was administered in the vapor phase at concentrations that produce aqueous concentrations at 37 degrees C of 0.4, 2.0, and 4.0 mM. Damage was assayed by leakage of aspartate transaminase and the inclusion of Trypan Blue immediately after the 2-hr incubation and after an additional 6-hr incubation in 20% O2. Only in the case of 0.5% O2 and 4 mM CCl4 were the monolayers damaged (18%) immediately after the 2-hr exposure; all other exposed cells were undamaged at that time point and the dose response of cell death as a function of CCl4 and oxygen concentration was not evident until the 6-hr time point. The monolayers exposed to 4 mM CCl4 and 1, 2, or 20% O2 exhibited little immediate damage but were all 100% dead 6 hr later. The monolayers exposed to 2 mM CCl4 and 0.5, 1, 2, or 20% O2 were 53, 48, 40, and 22 +/- 2% dead after 6 hr, respectively. These results suggest that effects of CCl4 exposure, for example alterations in the function or synthesis of essential proteins, require several hours to affect cell viability.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, California 94305-5117.
authors.forename: A K
authors.initials: AK
authors.lastname: Costa
authors.forename: J R
authors.initials: JR
authors.lastname: Trudell
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
chemical_list: D002251:Carbon Tetrachloride; D010100:Oxygen