Bilirubin toxicity in a neuroblastoma cell line N-115: II. Delayed effects and recovery.
Clinical studies have suggested that the early stages of bilirubin encephalopathy are reversible. These phenomena are investigated at the cellular level using the neuroblastoma cell line N-115 as a model system. To determine whether the cell line N-115 can recover from bilirubin toxicity, and whether the cellular function remains intact after a short period of bilirubin exposure during which time no toxic effects are manifest, the cells are exposed to bilirubin at varying concentrations and varying bilirubin:albumin ratios for 1 and 2 h. The bilirubin is then washed out, and the cells are reincubated in fresh media with appropriate amounts of albumin. Mitochondrial function, [3H]thymidine uptake and L-[35S]methionine uptake are assessed at 2, 8, and 24 h of reincubation after the bilirubin washout. After the short-term exposure, the cells begin to demonstrate evidence of toxicity in all parameters measured 8-24 h after the bilirubin washout. After the 2-h exposure to bilirubin, the cells demonstrate significant toxicity within 2 h of the bilirubin washout. The degree of toxicity seems to depend on the bilirubin:albumin ratio and bilirubin concentration. In general, after bilirubin exposure of 1 h or longer, the N-115 cells develop evidence of toxicity which is progressive and irreversible.
Amit
Y
Y
Department of Pediatrics, University of Alberta, Edmonton, Canada.
Poznansky
M J
MJ
Schiff
D
D
D000418:Albumins / Q000494:pharmacology; D000818:Animals; D001663:Bilirubin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007647:Kernicterus / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009447:Neuroblastoma / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000418:Albumins; D008715:Methionine; D001663:Bilirubin; D013936:Thymidine