ABSTRACT

If radiation biology has a dogma, it is that the deleterious effects of ionizing radiation result from the deposition of energy in the cell nucleus causing damage to a critical target (the nuclear DNA) with a major role assigned to the induction of DNA double-strand breaks. Radiation-induced cell death is attributable to failure to repair DNA damage resulting in cells which manifest residual DNA damage and die by mitotic failure or apoptosis. Surviving cells with misrepaired or unrepaired damage transmit changes to all descendant cells, i.e., the change is clonal. As malignant transformation is believed to be initiated by a gene mutation or a chromosomal aberration, the initiating lesion for malignant transformation has been similarly attributed to DNA damage in the directly irradiated cell. A litany of the results of early experiments which provided evidence for the nucleus as the sensitive target in the cell is part of the groundwork of any traditional radiation biology course or text as follows:

. Microbeam irradiation demonstrates the cell nucleus to be much more sensitive than the cytoplasm.