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This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of ‘practical’ threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye.Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40–50 years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower.A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1–1.2, and in a few cases 1.5–2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors.Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5 Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.

To determine how nature would protect lens epithelial cells from H2O2 stress, an immortal murine lens epithelial cell line, alphaTN4-1, was subjected to gradually increasing H2O2 levels over a period of approximately 8 months. The resultant conditioned cells grew normally when exposed daily to 125 microM H2O2, whereas normal cells died within 9 hours. This communication describes changes in the cell biology of the conditioned cells that allowed them to remain viable. The manner in which critical biochemical parameters were affected in both conditioned and normal cells is also reported.Conditioned cells were obtained by gradually increasing the concentration of H2O2 over a period of approximately 8 months, introducing an aliquot of H2O2 every 24 hours. A wide spectra of biological parameters were evaluated, including catalase, GSH peroxidase and other antioxidative enzyme activities, cell number and cell viability, non-protein thiol, ATP, transport systems, thymidine incorporation, and DNA cleavage.Surprisingly, the conditioned cells did not degrade the medium H2O2 more rapidly than normal cells. However, analyses of the antioxidative defenses indicated that catalase activity was increased 60-fold and glutathione peroxidase (GSH Px) approximately 2.7-fold. Glucose-6-phosphate dehydrogenase, GSH S-transferase, and GSSG reductase also had increased activity. Using one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, in situ trypsin digestion and matrix-assisted laser desorption/ionization mass spectrometry, a highly amplified doublet in the conditioned cell preparation was shown to be GSH S-transferase alpha-1 and alpha-2 isomers. Examination of key biochemical parameters indicated that while most such parameters in the conditioned cells showed marked decay in the first hour or so after stress, recovery was then observed and within a few hours, these parameters were back in the normal range. In contrast, damage in the normal cells was not repaired. The damage to DNA was shown to involve Fenton chemistry. In the presence of a metal ion chelator, normal cells survive H2O2 stress.The overall conclusion from this investigation is that nature has chosen to respond to the H2O2 stress by not only increasing the activity of enzymes degrading H2O2 but also the systems involved in repair, generation of reducing potential, and detoxification. All but one system of those evaluated appears to be permanently modified.

Three major 32P-labeled polypeptides were found in the soluble fraction of bovine lenses cultured in a medium containing [32P]orthophosphate. Two of the polypeptides corresponded to the phosphorylated A and B chains of alpha-crystallin. In this communication, the third polypeptide is now identified. This polypeptide is characterized by a molecular weight of 27,000 and a pI of 6.6, eluted exclusively in the beta Low fraction of a CL-6B gel filtration separation of lens soluble material, and could be further purified by DE52 anion exchange chromatography. The only 32P-labeled amino acid detected was phosphoserine. A single 32P-labeled peptide was observed after tryptic digestion and two-dimensional mapping. The amino acid sequence of the purified peptide is Gly-Ala-Phe-His-Pro-Ser-Ser. This sequence exactly matches the expected C-terminal tryptic fragment, residues 198-204, of the bovine beta-crystallin B2. The results of carboxypeptidase A digestion of the 32P-labeled peptide suggest that only Ser203 is phosphorylated. By using the catalytic subunit of the cAMP-dependent protein kinase, purified beta B2 was phosphorylated in vitro, generating a single 32P-labeled polypeptide with the identical pI as the phosphorylated polypeptide obtained from lens culture. On the basis of these data, the Mr 27,000 32P-labeled polypeptide is identified as the phosphorylated form of the beta-crystallin B2.