ABSTRACT
Exposure to high doses of ionizing radiation unequivocally produces adverse health effects including malignancy. At low doses the situation is much less clear, because effects are generally too small to be estimated directly by epidemiology, and extrapolation of risk and establishment of international rules and standards rely on the linear no-threshold (LNT) concept. Claims that low doses are more damaging than would be expected from LNT have been made on the basis of in vitro studies of nontargeted bystander effects and genomic instability, but relevant investigations of primary cells and tissues are limited. Here we show that after low-dose low-LET in vivo radiation exposures in the 0-100-mGy range of murine bone marrow there is no evidence of a bystander effect, assessed by p53 pathway signaling, nor is there any evidence for longer-term chromosomal instability in the bone marrow at doses below 1000 mGy. The data are not consistent with speculations based on in vitro nontargeted effects that low-dose X radiation is more damaging than would be expected from linear extrapolation.
Subject(s)
Bone Marrow Cells/radiation effects , Radiation Dosage , Animals , Apoptosis/radiation effects , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Bystander Effect/radiation effects , Chromosomal Instability/radiation effects , Dose-Response Relationship, Radiation , Linear Energy Transfer , Mice , Signal Transduction/radiation effects , Stress, Physiological/radiation effects , Time Factors , Tumor Suppressor Protein p53/metabolism , X-RaysABSTRACT
PURPOSE: To determine the role of single (SSB) and double strand break (DSB) repair in the induction and propagation of radiation-induced instability. MATERIALS AND METHODS: Two defined hamster cell lines with known DNA repair deficiencies in DSB repair (XR-C1) and base excision repair (EM-C11) and the parental wild-type line (CHO-9) were used. The rate of micronucleus formation, apoptosis and survival were measured at 0, 7 and 14 days after X-ray radiation. RESULTS: An enhanced rate of production of damaged cells was observed in wild type and the repair deficient mutants after irradiation. This was cell type, dose and time-dependent. All cells demonstrated delayed death up to day 14 after irradiation along with an elevated apoptosis frequency. The yield of micronuclei was not significantly increased in the wild-type cells, but was in the mutant cells, over the dose and time range studied. For all three endpoints the increase in damage was most pronounced in the SSB deficient cell line. CONCLUSIONS: SSB and/or oxidized base damage play a major role, rather than DSB, in radiation induced instability.
