Studies of non-disjunction of the major autosomes in Drosophila melanogaster. II. Effects of dose-fractionation, low radiation doses, EMS, and ageing.
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DNA double-strand breaks (DSBs) which arise in G1- or G0-phase normal human cells are repaired by nonhomologous end-joining (NHEJ), a pathway which is important for cell survival but can cause mutations at the break sites. DSB repair by NHEJ is very efficient at high damage levels of 1 or more DSBs per cell, much less efficient at lower damage levels and almost absent if only ~0.05 DSBs per cell are induced. Here, we have analyzed the repair of high and low levels of radiation-induced DSBs in primary fibroblasts from 136 childhood cancer survivors, half of whom developed a second independent tumor later in life, and compared it to the response of primary fibroblasts from 68 individually matched cancer-free individuals. We measured the DSB repair efficiency by quantifying residual γH2AX foci with an automated scoring system at 24 h after irradiation with doses of 2.5, 5, 10, and 100 mGy, which induce about 0.0625, 0.125, 0.25, and 2.5 DSBs per cell, respectively. Although childhood cancer survivors and cancer-free individuals repaired DSBs after 10 and 100 mGy equally efficiently, their response to lower doses differed drastically. While repair in cancer-free individuals was inefficient after 2.5 mGy, childhood cancer survivors repaired DSBs after this dose as efficiently as after higher doses. These results indicate that most of the childhood cancer survivors analyzed here may harbor a genetic alteration that affects their response to low levels of DSBs. We suggest that such alterations may be either inherited or caused by previous tumor treatments.
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Twenty-seven children with previously untreated Hodgkin's disease (CS I-2, II-13, III-3, IV-9) were given three cycles of MOPP to induce a remission which was consolidated with extended field radiation (2000--3500 rad) and three cycles of MOPP. Surgical staging was discontinued. Twenty-five of 27 children have not relapsed (range 15+--64+ months; median 39+ months); two children have died, one of uncontrolled Hodgkin's disease and one of acute infection while in complete remission. Actuarial 3 and 5 year survival rates and relapse-free rates are 91%. The merits of this treatment approach are discussed.
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Risk of breast cancer following radiation exposure was studied, based on surveys of tuberculosis patients who had multiple fluoroscopic examinations of the chest, mastitis patients given radiotherapy, and atomic bomb survivors. Analysis suggests that the risk is greatest for persons exposed as adolescents, although exposure at all ages carries some risk. The dose-response relationship was consistent with linearity in all studies. Direct evidence of radiation risk at doses under 0.5 Gy (50 rad) is apparent among A-bomb survivors. Fractionation does not appear to diminish risk, nor does time since exposure (even after 45 years of observation). The interval between exposure and the clinical appearance of radiogenic breast cancer may be mediated by hormonal or other age-related factors but is unrelated to dose. Age-specific absolute risk estimates for all studies are remarkably similar. The best estimate of risk among American women exposed after age 20 is 6.6 excess cancers/10(4) WY-G-Y (10(6) WY-rad).
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274 persons were examined by the provocation test of Heinz's bodies according to BEUTLER. 168 of them were working under x-rays exposure. No correlation could be identified between the dosage and the presence of Heinz's bodies in the lower range of the dosage related to the annual x-rays load and the integrated total exposure.
Objective: Long-term low-dose ionizing radiation may alter genomes and cause diseases. This study examined serum exosomal miRNA differences among radiation-exposed medical workers by work types. Methods: High-throughput sequencing screened serum exosomal miRNAs in diagnostic radiologists, interventional radiologists, and nuclear medicine doctors. qRT-PCR validated differentially expressed miRNAs. Results: 410 differentially expressed miRNAs, including 102 downregulated and 308 upregulated miRNAs, enriched in 15 KEGG pathways. Four miRNAs were validated. miR-30e-5p, miR-155-5p and miR-486-5p differed significantly among groups(P<0.01).The expression levels of these three miRNAs were lower in the nuclear medicine group than in the diagnostic group (0.25±0.05vs3.89±8.62,0.10±0.15vs7.03±15.75,0.37±0.39vs4.46±9.64;Z=3.542,3.335,9.859;P<0.01), whereas miR-155-5p was lower in the interventional group than in the diagnostic group(1.32±2.43vs 7.03±15.75;H=11.889,P=0.003), miR-486-5p was higher(9.54±19.39vs4.46±9.64; H=9.859,P=0.007). All four miRNAs showed higher expression in the 14-31-year work-experience group, and all four also showed age-dependent differences, with miR-30d-5p and miR-486-5p showing the age-related differences (P<0.01). Combined detection of the four miRNAs improved discrimination among occupational categories (AUC=0.784). Multiple linear regression analysis showed that sex was associated with all four miRNAs, whereas work type was associated with miR-30d-5p and miR-155-5p (P<0.05). Conclusion: Serum exosomal miR-30e-5p, miR-155-5p, and miR-486-5p are promising biomarkers for monitoring radiation-induced damage, supporting occupational protection and health management.