PHYSICAL INTERACTION OF IONIZING-RADIATIONS WITH THE INTRACELLULAR MACROMOLECULAR TARGET DNA AND ITS BIOLOGICAL CONSEQUENCES

Chromosomal DNA breaks were evaluated in normal human fibroblasts afte r irradiation of non-cycling G1 phase cells with 90 keV.mu m(-1) alpha particles and 250 kV(p) X rays. Yields were measured using the premat ure chromosome condensation technique in interphase cells, straight af ter and 24 h after irradiation, and by mitotic scoring of terminal del etions following cellular release at 24 h and progression through the cell cycle. Yields were related to the frequencies of energy depositio n events per cell nucleus estimated microdosimetrically for X rays and by relating fluence to nuclear cross-sectional areas for the alpha pa rticles. Linear relationships were found for both radiations and at al l three times post-irradiation Initial break yields of 1.3 x 10(0) and 1.6 x 10(-2) per energy deposition event for alpha particles and X ra ys 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) a nd 4.0 x 10(-5) per energy deposition event. That is, one 90 keV.mu m( -1) alpha particle is about 100 times more biologically effective than an electron track from 250 kV(p) X rays and greater than 99% of initi ally induced chromosomal DNA breaks are repaired/misrepaired before th e next mitosis. Misrepair will involve illegitimate interactions and c ombinations of pairs of lesions, entities which pre-dominate at mitosi s, while a failure to repair/misrepair resulting in relic DNA double s trand breaks is likely to be of minimal consequence. Lesion interactio n, proximity dependent, and largely irrespective of LET dependent lesi on severity will then be the principal basis for the unwanted biologic al sequelae from ionising radiations.