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.