Accumulation of Chromosome Damage under Continuous Low Dose Rate Exposure

Abstract

Various renewal tissues of the body can maintain function and a steady level of cell population for relatively long periods under high dose rates of continuous irradiation, apparently indicating no serious accumulation of damage affecting cell proliferation. The epithelium of the small intestine can maintain function and a steady cell population at dose rates as high as 400 rads/day, the bone marrow only at doses of 50 rads/day or less, while collapse with progressive cellular depopulation will occur in the testis after a few rads per day (14). In rapidly dividing renewal systems, there is an effective selection-out of damaged cells as well as repair of sublethal damage affecting proliferation. In a more slowly dividing system, such as the liver, there is also apparently some repair or elimination of radiation damage. The pattern of cell proliferation after partial hepatectomy is relatively little disturbed by prior exposure to dose rates of from 16 to 70 rads/day, in spite of the accumulation of large radiation doses and in the presence of considerable chromosome injury. There is a delay in onset of DNA synthesis and cell division in the parenchymal cell population which appears to be dependent on the dose rate, the duration of exposure, and the accumulated dose. At higher dose rates and after long periods of irradiation, there is (a) a decrease in the rate of entry of cells into synthesis and mitosis; (b) a decrease in the number of cells taking part in the regenerative process; (c) an increase in the overall duration of cell proliferation during regeneration, and (d) an increase in the number of observable chromosome aberrations and possibly of polyploid parenchymal cells (9–11). A radiation effect in the nonproliferating liver that becomes manifest only upon proliferation is the production of chromosome aberrations (1, 2, 5, 6, 16, 17, 20, 21, 24, 26). Following CCl4-induced liver regeneration in rats, the yield of spontaneous aberrations increases with age and the number of radiation-induced chromosome injuries decreases with time. These effects are observed two hundred and fifty days after a single exposure or after multiple hepatectomies. The decrease is less marked than the proliferative inhibition, however, and the rate of reduction is greater than could be explained by the elimination of injured chromosomes at cell division (1, 2, 7, 16, 24). After continuous exposure, the frequency increases faster than in unirradiated controls, but not as fast as would be predicted from single-dose experiments (5, 7, 21, 22). The accumulation of chromosomal or other nonlethal cellular damage under continuous irradiation in the stem-cell compartment of slowly proliferating tissues is one of the major factors which might affect the regenerative capacity of the precursor cell population and its ability to deal with chronic stress.