Effects of heavy ions on rabbit tissues: induction of DNA strand breaks in retinal photoreceptor cells by high doses of radiation.

Abstract

Excised retinas from New Zealand white (NZW) rabbits were irradiated at 0 degrees C with 9-260 Gy (depending on the type of radiation) of 300 kVp X-rays, or the first 5 cm (range: approximately 14 cm in water) of 365 MeV/u Ne ions or 530 MeV/u Ar ions (LET infinity's: approximately 1, 35 +/- 3 and 90 +/- 5 keV/micron, respectively). Other positions (LET infinity's) in the Ne-ion beam (Bragg curve) were employed in more limited experiments. The retinas were frozen and stored in liquid nitrogen until analysis. Total strand breakage in the DNA of retinal photoreceptor (sensory) cells was determined from sedimentation profiles obtained by velocity sedimentation through reoriented alkaline sucrose gradients under conditions free from anomalies related to rotor speed. For the radiation doses employed: the reciprocal of the number average molecular weight, Mn, was related linearly to dose for each radiation quality and extrapolation to zero dose in each case gave positive intercepts for which the mean unirradiated molecular weight, M0, was 6.1 +/- 1.0 X 10(8) daltons; the efficiencies of total strand breakage for the different radiations were 50 +/- 3, 110 +/- 2 and 240 +/- 6 eV/strand break, respectively. For the heavy ions, accurate analogous calculations for other positions in the Bragg curves were precluded by beam degeneration due to fragmentation of the primary particles, etc. Overall, the experimental results support the concept that ionizing radiations damage cellular DNA by two general processes. One process causes localized damage, which under our experimental conditions is revealed as strand breaks and/or alkali-labile bonds in regions between molecules of size circa 10(9) daltons (subunits); the other causes essentially random damage. Base damage caused by either process would not have been delineated in our experiments.