Physical interaction ionising radiations with the intracellular macromolecular target DNA and its biological consequences

Chromosomal DNA breaks were evaluated in normal human fibroblasts after irradiation of non-cycling G1 phase cells with 90 keV.μm^-1 α a particles and 250 kV(p) X rays. Yields were measured using the premature chromosome condensation technique in interphase cells, straight after and 24 h after irradiation, and by mitotic scoring of terminal deletions following cellular release at 24 h and progression through the cell cycle. Yields were related to the frequencies of energy deposition events per cell nucleus estimated microdosimetrically for X rays and by relating fluence to nuclear cross-sectional areas for the a particles. Linear relationships were found for both radiations and at all three times post-irradiation. Initial break yields of 1.3 x 10⁰ and 1.6 x 10^-2 per energy deposition event for a particles and X rays respectively, changed to residual yields (24 h) of 4.0 x 10^-1 and 1.3 x 10^-3, and for terminal deletions at mitosis to 6.0 x 10^-3 and 4.0 x 10^-5 per energy deposition event. That is, one 90 keV.μm^-1 a particle is about 100 times more biologically effective than an electron track from 250 kV(p) X rays and greater than 99% of initially induced chromosomal DNA breaks are repaired/misrepaired before the next mitosis. Misrepair will involve illegitimate interactions and combinations of pairs of lesions, entities which pre-dominate at mitosis, while a failure to repair/misrepair resulting in relic DNA double strand breaks is likely to be of minimal consequence. Lesion interaction, proximity dependent, and largely irrespective of LET dependent lesion severity will then be the principal basis for the unwanted biological sequelae from ionising radiations.