CELLULAR MECHANISMS OF PROTECTION AND REPAIR INDUCED BY RADIATION EXPOSURE AND THEIR CONSEQUENCES FOR CELL SYSTEM RESPONSES

The complex biological systems that constitute living organisms operat e at various levels of organization, from the atomic-molecular to the cellular to the organ-organism level. The response of an organism to d isturbances that are detrimental to structure and function generally b egin at the level of organization where the primary injury has occurre d. Detriment that occurs from simultaneous or sequential, or single or multiple interactions at a relatively low level of organization tends to be transferred to higher levels. However, at each level of organiz ation there is a given probability of such detriment being removed acc ording to the tolerance to injury that is peculiar to that level. Ther e is thus a direct relationship between the frequency of injurious eve nts at a lower level of organization, and the degree of structural com plexity of the system at the high level at which such detriment is eve ntually manifested. The extent of structural disruption at any given l evel determines the degree of functional failure at that level. In the exposure of tissue to ionization radiation, the primary injury begins with energy deposition events (tracks or hits) consisting of many ion izations and excitations in localized clusters of submicroscopic dimen sions at the atomic-molecular level of organization within the cell, a nd the cell is affected as a whole. The cell is the elementary unit of life and the sum of the individual cell responses determines the resp onse of the tissue and the organism. Individual cell responses are nev ertheless found to differ in type and degree depending on the absorbed dose. With decreasing values of absorbed dose to the tissue, the prob ability of a cell being hit by an energy deposition event decreases li nearly. At very low values of absorbed dose to tissue, only a fraction of the total cell population experiences single hits and these are of different sizes. The size distribution or spectrum of these hits is i nvariant, independent of their total number over a considerable range at low-dose levels and is determined only by the type and quality of t he given radiation. The probability that a hit cell will suffer a give n detriment such as a chromosomal aberration, gene mutation or death h as been shown to increase in a sigmoid fashion with increasing hit siz e. From the risk coefficient reported from leukemia in Japanese bomb s urvivors from low linear energy transfer (LET) exposure, the probabili ty of malignant transformation in the human hemopoietic stem cell suff icient to cause the death of the individual from leukemia has been cal culated to be approximately 10 E-14 per average hit. On the other hand , for low LET radiation there appears to be a probability of benefit f or the hit cell, at least in terms of a temporary stimulation of the c ellular systems for free radical detoxification and DNA repair. The de gree of temporary stimulation of radical detoxification has been seen in mouse bone marrow to increase to a maximum at an absorbed dose near 0.2 Gy, and may approach a probability of one per hit on average. Imp roved radical detoxification and DNA repair are both taken to enhance the cell's capacity to protect itself against spontaneously occurring detriment coming from free radicals that derive from oxidative metabol ism.