CHROMATIN STRUCTURE AND CELLULAR RADIOSENSITIVITY - A COMPARISON OF 2HUMAN TUMOR-CELL LINES

The role of variation in susceptibility to DNA damage induction was st udied as a determinant for cellular radiosensitivity. Comparison of th e radiosensitive HX142 and radioresistant RT112 cell lines previously revealed higher susceptibility to X-ray-induced DNA damage in the sens itive cell line using non-denaturing elution, but not when using alkal ine unwinding. The present data also show that no difference in the am ount of initial damage is seen when pulsed-field gel electrophoresis ( PFGE) or comet analysis are used for DNA damage assessment. However, u sing the halo assay or a modified version of PFGE in which the higher DNA architecture remained partially intact, the radiosensitive cells s howed steeper dose-response curves for initial DNA damage than the rad ioresistant cells. Analysis of the protein composition of DNA-nucleoid structures revealed substantial differences when isolated from HX142 or RT112 cells. From our data, it is concluded that HX142 and RT112 di ffer in their structural organization of chromatin. As no differences in the kinetics of DNA damage rejoining were found, it is hypothesized that the same amount of lesions have a different impact in the two ce ll lines in that the 'presentation' of DNA damage alters the ratio of repairable to non-repairable DNA damage.