Dose-effect relations for cell transformation and reproductive death induced in C3H/10T1/2 cells, NBCH-3 cells, and WAGR-2 cells by 300 kV X rays and monoenergetic fast neutrons of 0.5, 4.2, and 15 MeV energy have been analyzed on the basis of the relations F(D) = t1D + t2D2 and S(D)/S(0) = exp - (a1D + a2D2), respectively. Values of a1 are a factor of about 10(3) larger than corresponding values of t1, while the dependence on neutron energy is similar for both effects. RBE values and relations between the a1 and t1 values are compared with characteristics, derived from corresponding parameters for chromosome aberrations and reproductive death, induced in other cell lines after irradiation with the same neutron beams. A hypothesis is developed assuming that nonrandom structural changes at a restricted number of sites on one or more chromosomes are the primary causes of transformation of cultured mammalian cells by ionizing radiations, whereas similar but randomly distributed chromosomal changes, which are induced at many sites on all chromosomes, cause observable aberrations and reproductive death. Flow cytometry of chromosome suspensions has been used to demonstrate nonrandom changes of chromosomes in selected clones of transformed cells and of random changes of chromosomes in cells inactivated by X rays and neutrons.
The effects of multifraction irradiation with X rays, neutrons, and pions on the rat cervical and lumbar spinal cord, mouse lung, and rat rectum have been investigated. The linear-quadratic model was used to analyze the effectiveness per unit dose for various tissue responses. It is concluded that the dependence of tolerance doses on fraction size is considerably reduced for both intermediate (pions) and high-LET (neutrons) radiations, as shown by the observed alpha/beta ratios in the range of 20-50. With accurately defined alpha/beta values for various tissues and types of radiation, the same tolerance formalisms can be used as proposed for low-LET radiation. The effectiveness of pion irradiation shows a significant dependence on dose rate when treatment times are long and repair of subeffective damage occurs during the irradiations. For late effects in spinal cord, lung, and rectum, RBE values of pions are 1.5 or less at doses per fraction in the range of 1.2-4.5 Gy.
In the past cellular fast-mixing techniques have been used to investigate the time resolution of radiation processes that lead to modification of radiation response in bacterial and mammalian cellular systems. So far, published studies have been confined to effects with low-LET electron beams. The brief for this paper was to discuss where, and under what conditions, such a technique could be used to advantage with high-LET particle beams. Criteria for the experimental design, including conditions of flow rate, dose rate, and mixing times, are discussed. Radiobiological problems appropriate for applications of fast-particle beams are also discussed. These include studies to reveal possible multicomponents in cellular sensitization by oxygen and electron-affinic radiation sensitizers, studies designed to assist in the resolution of direct and indirect effects, and resolution of intracellular DNA damage.
Two sets of observations on cataractogenesis in the New Zealand white (NZW) rabbit (Oryctolagus cuniculus) following localized exposure of optic and proximate tissues to heavy ions are reported. The experiments involved measurements of lenticular opacification in young (ca. 9 weeks old) rabbits caused by graded doses (0.5-5.0 Gy) of 460 MeV/u (incident energy) 56Fe ions and the effects of animal age (9 +/- 0.3 week, 1 +/- 0.5 year, and 4.5 +/- 1.3 year) on lenticular opacifications caused by 9 Gy of 400 MeV/u (incident energy) 20Ne ions. In substantiation of earlier results from NZW rabbits exposed to other low- and high-LET radiations, there was a dose-dependent onset of cataractogenesis following 56Fe-ion irradiation, with the highest doses causing the earliest appearance of cataracts. The level of stationary cataracts was also dependent on dose, and preliminary estimates of RBE yield values comparable to those found at similar doses (0.5-5.0 Gy) by others with populations of cultured cells. With increasing age at the time of exposure to 20Ne ions, the onset of lenticular opacification was delayed progressively and the level of stationary cataracts was reduced, but the onset and progression of late cataractogenesis was most rapid in the oldest group of animals. A discussion of the use of cataract measurements in risk assessment is included in this article.

