Chromatin compaction and tumor cell radio sensitivity at 2 gray

Mammalian cells at mitosis, differentiated lymphocytes, and some radiation- hypersensitive mutants in interphase contain all or a measurable portion of their chromatin in condensed/ compacted form and are hypersensitive to ion izing radiation by the mechanism described by single-hit inactivation kinet ics (a). These observations led to the investigation as to whether compacte d chromatin in interphase is the target that determines the widely variable a-parameters and surviving fractions of 2 Gy (SF2Gy) measured for human tu mor cell lines. Six cell lines whose SF2(Gy) ranged from 0.29 to 0.73 were used for this study. Their different radiosensitivities were associated mai nly with differences in their single-hit inactivation parameters (a). Elect ron microscope images of interphase nuclei were optically scanned, and the pixel densities were digitized for quantitative analyses. A significant cor relation between the percentage of nuclear pixels with densities similar to those found in mitotic chromosomes (percent compacted chromatin) and the a lpha -inactivation parameters was observed. Digital analyses of electron an d/or confocal microscope images of chromatin in interphase tumor cells in b iopsy specimens could become a rapid assay for predicting the intrinsic rad iosensitivity of tumor clonogens. This research has also identified some in hibitors of protein (historic) phosphatases that promote chromatin compacti on and radiosensitize cells to 2-Gy dose fractions.