Chromosome Translocations and Cosmic Radiation Dose in Male U.S. Commercial Airline Pilots.

BACKGROUND: Chromosome translocations are a biomarker of cumulative exposure to ionizing radiation. We examined the relation between the frequency of translocations and cosmic radiation dose in 83 male airline pilots. METHODS: Translocations were scored using fluorescence in situ hybridization chromosome painting. Cumulative radiation doses were estimated from individual flight records. Excess rate and log-linear Poisson regression models were evaluated. RESULTS: Pilots' estimated median cumulative absorbed dose was 15 mGy (range 4.5-38). No association was observed between translocation frequency and absorbed dose from all types of flying [rate ratio (RR) = 1.01 at 1 mGy, 95% confidence interval (CI) 0.97-1.04]. However, additional analyses of pilots' dose from only commercial flying suggested an association (RR = 1.04 at 1 mGy, 95% CI 0.97-1.13). DISCUSSION: Although this is the largest cytogenetic study of male commercial airline pilots to date of which the authors are aware, future studies will need additional highly exposed pilots to better assess the translocation-cosmic radiation relation.Grajewski B, Yong LC, Bertke SJ, Bhatti P, Little MP, Ramsey MJ, Tucker JD, Ward EM, Whelan EA, Sigurdson AJ, Waters MA. Chromosome translocations and cosmic radiation dose in male U.S. commercial airline pilots. Aerosp Med Hum Perform. 2018; 89(7):616-625.

Diagnostic X-ray examinations and increased chromosome translocations: evidence from three studies.

Controversy regarding potential health risks from increased use of medical diagnostic radiologic examinations has come to public attention. We evaluated whether chromosome damage, specifically translocations, which are a potentially intermediate biomarker for cancer risk, was increased after exposure to diagnostic X-rays, with particular interest in the ionizing radiation dose-response below the level of approximately 50 mGy. Chromosome translocation frequency data from three separately conducted occupational studies of ionizing radiation were pooled together. Studies 1 and 2 included 79 and 150 medical radiologic technologists, respectively, and study 3 included 83 airline pilots and 50 university faculty members (total = 155 women and 207 men; mean age = 62 years, range 34-90). Information on personal history of radiographic examinations was collected from a detailed questionnaire. We computed a cumulative red bone marrow (RBM) dose score based on the numbers and types of X-ray examinations reported with 1 unit approximating 1 mGy. Poisson regression analyses were adjusted for age and laboratory method. Mean RBM dose scores were 49, 42, and 11 for Studies 1-3, respectively (overall mean = 33.5, range 0-303). Translocation frequencies significantly increased with increasing dose score (P < 0.001). Restricting the analysis to the lowest dose scores of under 50 did not materially change these results. We conclude that chromosome damage is associated with low levels of radiation exposure from diagnostic X-ray examinations, including dose scores of approximately 50 and lower, suggesting the possibility of long-term adverse health effects.

Cigarette smoking during pregnancy: chromosome translocations and phenotypic susceptibility in mothers and newborns.

The effects of maternal cigarette smoking during pregnancy on structural chromosome aberrations were evaluated in peripheral lymphocytes from 239 mothers and their 241 newborns to determine whether smoking during pregnancy, genetic susceptibility, and race are associated with chromosome aberrations including translocations. Demographic information and cigarette smoking data were obtained via questionnaire. There were 119 Caucasian Americans, 118 African Americans, and 2 Asian Americans. The average maternal age was 24.9+/-5.8 (mean+/-S.D.) years. Thirty-nine percent of the Caucasian Americans and 45.4% of the African Americans self-reported that they were active smokers during the index pregnancy. The average number of cigarettes smoked per day was 2.65+/-5.75 and 1.37+/-3.17 for Caucasian and African American mothers, respectively. Peripheral blood lymphocytes from the mother and from the fetal side of the placenta were evaluated for chromosome aberrations by whole chromosome painting. Aliquots from the same blood samples were also used to assess genetic susceptibility with an in vitro bleomycin challenge assay. Spontaneous translocation frequencies in both maternal and newborn lymphocytes were not associated with cigarette smoking, socioeconomic status, or education. The absence of a smoking effect may be attributable to the low level of cigarette usage in these subjects. The average bleomycin-induced damage in the maternal and newborn populations was 0.37+/-0.27 and 0.15+/-0.14 breaks per cell, respectively, a difference that was highly significant (p<0.0001). In newborns there was a positive association between bleomycin sensitivity and the frequencies of aberrations as measured by chromosome painting: p

Persistence of chromosome aberrations following acute radiation: II, does it matter how translocations are scored?

Chromosome breaks and rearrangements resulting from ionizing radiation can be much more complicated than many investigators thought possible some years ago. The realization that not all translocations are reciprocal, that multiway exchanges occur, and that some double-strand breaks are not repaired prior to mitosis have all contributed to the difficulty of knowing how best to identify, record, evaluate, and report chromosome translocations. Here we describe the results of a series of experiments in which blood from two normal healthy subjects was obtained, irradiated with 137Cs gamma-rays in vitro at doses ranging from 0 (controls) to 4 Gy, and cultured. Cells from each dose group and donor were harvested at days 2, 2.5, 3, 4, 5, and 7 and evaluated for chromosome damage by simultaneously painting chromosomes 1, 2, and 4 in red and 3, 5, and 6 in green. The persistence of dicentrics, fragments, rings, insertions, and PAINT translocations are reported separately by us in this issue. In this article, we focus on translocations, characterizing the various types in detail and comparing and contrasting their persistence across all dose groups for both donors. The results indicate that the persistence of all translocation types was sufficient to be used for retrospective dosimetry, although nonreciprocal translocations exhibited diminished persistence compared to the other types. We also characterize the kinetics of the radiation dose responses of the two donors who exhibited significant differences in the induction as well as the persistence of translocations. Based on the evidence presented here, we hypothesize that these individuals differ in the recognition and repair of radiation-induced damage as well as in cell cycle checkpoint control. Despite these differences, the temporal frequency of translocation losses at both the high and low doses was similar for both subjects.

Persistence of chromosome aberrations following acute radiation: I, PAINT translocations, dicentrics, rings, fragments, and insertions.

Chromosome translocations are used to estimate the doses of radiation received following occupational or accidental exposure. Biodosimetry relies on the assumption that translocations are not cell-lethal and persist with little or no loss over time. While translocations do exhibit substantially greater persistence than other aberration types (e.g., dicentrics), there is evidence that translocation frequencies also decline over time, at least following acute doses above 1 Gy. To the extent that translocation frequencies decline, the predicted absorbed doses will be underestimated. Yet unknown is whether translocations induced by ionizing radiation at doses below 1 Gy also show significant declines. Here we report on the persistence of translocations induced by 137Cs gamma-rays at acute doses ranging from 0.2 to 4 Gy using peripheral blood lymphocytes from two unrelated healthy male donors. Chromosome aberrations were evaluated by simultaneously painting chromosomes 1, 2, and 4 in red and 3, 5, and 6 in green in cells harvested 2-7 days following exposure and were scored using the PAINT system. Translocations were also enumerated using several other methods and these results are reported separately by us in this issue. For comparison, the persistence of dicentrics, rings, acentric fragments, and color junctions was also evaluated and showed rapid losses with time. The results from both donors provide evidence that translocation frequencies decline with time in a statistically significant manner at doses as low as 0.2-0.3 Gy. The frequency of translocations for all dose groups declined from day 2 to 7 by averages of 39% and 26% for donors 1 and 2, respectively. These data emphasize the importance of considering translocation loss in biological dosimetry long times after exposure.

Persistence of chromosome aberrations in mice acutely exposed to 56Fe+26 ions.

Space exploration has the potential to yield exciting and significant discoveries, but it also brings with it many risks for flight crews. Among the less well studied of these are health effects from space radiation, which includes the highly charged, energetic particles of elements with high atomic numbers that constitute the galactic cosmic rays. In this study, we demonstrated that 1 Gy iron ions acutely administered to mice in vivo resulted in highly complex chromosome damage. We found that all types of aberrations, including dicentrics as well as translocations, insertions and acentric fragments, disappear rapidly with time after exposure, probably as a result of the death of heavily damaged cells, i.e. cells with multiple and/or complex aberrations. In addition, numerous cells have apparently simple exchanges as their only aberrations, and these cells appear to survive longer than heavily damaged cells. Eight weeks after exposure, the frequency of cells showing cytogenetic damage was reduced to less than 20% of the levels evident at 1 week, with little further decline apparent over an additional 8 weeks. These results indicate that exposure to 1 Gy iron ions produces heavily damaged cells, a small fraction of which appear to be capable of surviving for relatively long periods. The health effects of exposure to high-LET radiation in humans on prolonged space flights should remain a matter of concern.

Multi-endpoint biological monitoring of phosphine workers.

The pesticide phosphine (PH(3)) is a suspected carcinogen and a known clastogen which has been shown to produce chromosome damage in agricultural workers. To confirm and extend these results we evaluated 22 phosphine appliers and 26 controls matched for age and smoking status. Two independent methods were used to evaluate exposure: fluorescence in situ hybridization (FISH) with whole-chromosome paints of chromosomes 1, 2, and 4 labeled in a single color to quantify translocations in peripheral lymphocytes, and the glycophorin A (GPA) assay to quantify phenotypically mutant (NØ or NN) erythrocytes. No differences in the frequency of translocations were found in the phosphine appliers compared to the controls, and no effect of cigarette smoking was observed. However, a significant increase in the frequency of translocations with age (P<0.0001) was seen. No effect of phosphine exposure or cigarette smoking was observed in the GPA assay. These results are in contrast to previous findings from this same population which showed an increase in chromosome aberrations among phosphine appliers. The results are most easily interpreted as supporting the effectiveness of the personal protective equipment that is now worn by the workers but which was not employed prior to and during the earlier studies.

Three somatic genetic biomarkers and covariates in radiation-exposed Russian cleanup workers of the chernobyl nuclear reactor 6-13 years after exposure.

Three somatic mutation assays were evaluated in men exposed to low-dose, whole-body, ionizing radiation. Blood samples were obtained between 1992 and 1999 from 625 Russian Chernobyl cleanup workers and 182 Russian controls. The assays were chromosome translocations in lymphocytes detected by FISH, hypoxanthine phosphoribosyltransferase (HPRT) mutant frequency in lymphocytes by cloning, and flow cytometic assay for glycophorin A (GPA) variant frequency of both deletion (N/Ø) and recombination (N/N) events detected in erythrocytes. Over 30 exposure and lifestyle covariates were available from questionnaires. Among the covariates evaluated, some increased (e.g. age, smoking) and others decreased (e.g. date of sample) biomarker responses at a magnitude comparable to Chernobyl exposure. When adjusted for covariates, exposure at Chernobyl was a statistically significant factor for translocation frequency (increase of 30%, 95% CI of 10%-53%, P = 0.002) and HPRT mutant frequency (increase of 41%, 95% CI of 19%-66%, P < 0.001), but not for either GPA assay. The estimated average dose for the cleanup workers based on the average increase in translocations was 9.5 cGy. Translocation analysis is the preferred biomarker for low-dose radiation dosimetry given its sensitivity, relatively few covariates, and dose-response data. Based on this estimated dose, the risk of exposure-related cancer is expected to be low.