Cellular and tissue responses to heavy ions: Basic considerations

Abstract

Responses of the S/S variant of the L5178Y murine leukemic lymphoblast, the photoreceptor cell of the rabbit retina and the lenticular epithelium of the rabbit to heavy ions (20Ne, 28Si, 40Ar and 56Fe) are described and discussed primarily from the standpoint of the need for a comprehensive theory of cellular radiosensitivity from which a general theory of tissue radiosensitivity can be constructed. The radiation responses of the very radiosensitive, repair-deficient S/S variant during the G1- and early S phases of the cell cycle were found to be unlike those of normally radioresistant cells in culture: the relative biological effectiveness (RBE) did not increase with the linear energy transfer (LET infinity) of the incident radiation. Such behavior could be anticipated for a cell which is lacking the repair system that operates in other (normal) cells when they are exposed to ionizing radiations in the G1 phase of the cell cycle. The S/S variant does exhibit a peak of radioresistance to X-photons mid-G1 + 8 h into the cell cycle, however, and as the LET infinity was increased, the repair capacity responsible for that radioresistance was reduced progressively. Sensory cells (photoreceptors) in the retina of the New Zealand white (NZW) rabbit are very radioresistant to ionizing radiations, and several years elapsed after localized exposure (e.g., 5-10 Gy) to heavy ions (20Ne, 40Ar) before photoreceptor cells were lost from the retina. During the first few weeks after such irradiations, damage to DNA in the photoreceptor cells was repaired to a point where it could not be demonstrated by reorienting gradient sedimentation under alkaline conditions, a technique that can detect DNA damage produced by less than 0.1 Gy of X-photons. Restitution of DNA structure was not permanent, however, and months or years later, but before loss of photoreceptor cells from the retina could be detected, progressive deterioration of the DNA structure began. Age dependencies of late sequelae from densely ionizing radiations are matters of concern both for the therapeutic uses of radiation and the risk/benefit considerations of environmental exposure, especially in outer space. A pilot experiment with a single acute exposure to 20Ne ions has illustrated the need for careful examination of the role of animal age at the time of irradiation in subsequent tissue responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Repair of DNA damage induced by accelerated heavy ions—A mini review

“…An example of chromosome repair with normal and repair defective cells using high‐LET heavy ions is shown here 62. It has been shown that RBE reaches unity for cell killing in nonhomologous end joining (NHEJ) defective cells irradiated with high‐LET heavy ions 106–109. The cytogenetic difference was also greatly diminished between normal and NHEJ defective cells after high LET exposure 62.…”

Relative biological effects of neutron mixed-beam irradiation for boron neutron capture therapy on cell survival and DNA double-strand breaks in cultured mammalian cells

“…For ionizing radiation, the RBE value increases with linear energy transfer (LET), peaks (around 100 − 200 keV/μm), and then decreases for DNA repair-proficient cells, whereas the RBE value constantly decreases with LET in repair-deficient cells [22, 23]. Neutrons with relatively high energy are classified as high-LET radiation, and it has been shown that neutrons have various high RBE values [4, 7, 10, 11].…”

The nature and possible mechanisms of potential mutations formation due to the appearance of tymine dimers after irradiating two-stranded DNA by ultra-violet light

“…Так, например, показано, что удаление бре шей репарационными механизмами происходит с полувременами 2; 15 и 160 мин [130]. В неделящихся клетках кролика восстановление поврежден ной ДНК до обычного размера хромосомы может занимать почти месяц [131]. Кинетика репарации поврежденных оснований может происходить с та кой же скоростью, как и репарация брешей [132,133].…”

“…Кинетика репарации поврежденных оснований может происходить с та кой же скоростью, как и репарация брешей [132,133]. Аналогичные времена жизни получены для дрожжей [131]. Характерные времена процессов, важных при образовании потенциальных мута ций, -это всегда доли секунды.…”