Association among DNA/chromosome break rejoining rates, chromatin structure alterations, and radiation sensitivity in human tumor cell lines

Abstract

The basis for radioresistance and radiosensitivity in human tumor cell lines is unknown. In a previous study, radiosensitivity in human tumor cell lines was found to be a function of the rate of DNA double-strand break rejoining. Radioresistant cell lines rejoined DNA double-strand breaks at a faster rate than more sensitive cell lines. In this study, we have expanded on that work and analyzed the rate of chromosome break rejoining, as well as the type and frequency of chromosome aberrations induced in three relatively radioresistant (D0 greater than 2.0 Gy) human squamous cell carcinoma cell lines and three relatively radiosensitive (D0 less than 1.5 Gy) squamous cell carcinoma cell lines. Radioresistant cells were found to rejoin chromosome breaks faster than more sensitive cells. The faster rate of rejoining was associated with a reduced frequency of misrepair events (chromosome exchange-type aberrations) and greater survival. There were qualitative differences between these two groups of cell lines in their ability to bind ethidium bromide as nucleoids, suggesting that the basis for altered break rejoining rates might be related to chromatin structure.