Recovery of growth-arrested human fibroblasts from UV-induced lethal damage is inhibited by low cell density or sodium butyrate

Abstract

The influence of growth arrest on recovery from UV-induced lethal damage in human fibroblasts was investigated. Cells were arrested in G 1 either by confluent holding (high cell density at 37°C) or by temperature holding (low cell density at 3°C) or by combination of both methods. These experiments showed that survival recovery only occured in cells arrested at high cell density, both at 37°C and at 30°C, and not in cells arrested at low cell density at 30°C. Furthermore, it was demonstrated that the rate of transcription in unirradiated cells arrested at high density, both at 37°C and at 30°C, was much lower compared to that in cells arrested at low density. These observations can be explained by assuming that impaired transcription is responsible for UV-induced cytotoxicity and that recovery of RNA synthesis due to repair of damage in transcriptionally active genes may account for survival recovery. Sodium butyrate did not influence the absence of recovery during low temperature holding at low density but inhibited survival recovery during confluent holding. Sodium butyrate might prevent survival recovery at high cell density by inducing a chromatin structure resembling that of untreated cells arrested at low density.