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Chromosome translocations in peripheral blood lymphocytes of normal, healthy humans increase with age, but the effects of gender, race, and cigarette smoking on background translocation yields have not been examined systematically. Further, the shape of the relationship between age and translocation frequency (TF) has not been definitively determined. We collected existing data from 16 laboratories in North America, Europe, and Asia on TFs measured in peripheral blood lymphocytes by fluorescence in situ hybridization whole chromosome painting among 1933 individuals. In Poisson regression models, age, ranging from newborns (cord blood) to 85 years, was strongly associated with TF and this relationship showed significant upward curvature at older ages versus a linear relationship (p<0.001). Ever smokers had significantly higher TFs than non-smokers (rate ratio (RR)=1.19, 95% confidence interval (CI), 1.09-1.30) and smoking modified the effect of age on TFs with a steeper age-related increase among ever smokers compared to non-smokers (p<0.001). TFs did not differ by gender. Interpreting an independent effect of race was difficult owing to laboratory variation. Our study is three times larger than any pooled effort to date, confirming a suspected curvilinear relationship of TF with age. The significant effect of cigarette smoking has not been observed with previous pooled studies of TF in humans. Our data provide stable estimates of background TF by age, gender, race, and smoking status and suggest an acceleration of chromosome damage above age 60 and among those with a history of smoking cigarettes.

Stable and unstable chromosome aberrations in human lymphocytes exposed to 2 and 4Gy of X-rays in G(0) were analyzed in M1 and M2 cells harvested at 72h to investigate how the scoring protocol influences the yields of aberrations transmitted through one mitosis. Metaphase chromosomes 2, 3, and 5 were painted using fluorescence in situ hybridization (FISH) whole chromosome probes, together with a pan-centromeric probe and stained by the harlequin-FISH method, to allow the cell cycle status of each cell to be determined as it was scored. A strict scoring criterion was adopted so that each metaphase had to contain 46 centromeres and each dicentric/centric ring had to have an acentric present. In addition to scoring the painted material, unstable aberrations in the whole genome were also recorded. The yield of complete dicentrics decreased by more than a factor of 2 in going from M1 to M2. The decrease was greater at the lower dose. Two-way translocations appeared stable, but one-way translocations decreased. This suggests that if translocation yields are to be used for biological dosimetry purposes, then the two-way type should be used.

This paper addresses a report of a large increase (approximately 6- to 11-fold) in chromosome aberrations in lymphocytes of persons in Salzburg attributed to their exposure to fallout from the Chernobyl cloud. Their additional exposure, approximately 0.3 mGy in 1 year, comprised about a 30% increase in their normal background radiation dose. The report has attracted considerable attention because, if correct, it seriously challenges assumptions of linearity in the low-dose response for chromosomal damage and, by implication, the linear, no-threshold hypothesis for risk of induced cancer. An experiment has been carried out with Syrian hamsters treated with caesium-137 to produce a range of doses comparable with those calculated for the persons in Salzburg. No significant elevation in lymphocyte aberration yields was found in the hamsters, thus arguing against the conclusions of the Salzburg study.

Assays for sister-chromatid exchanges (SCE), unstable chromosome and chromatid aberrations and micronuclei were performed on blood lymphocytes from persons exposed protractedly to radiation or chemical hazards in the workplace. There was a general tendency with all endpoints examined for the yields to increase with years of working in the industry. This was especially marked for SCE. By comparison with a control group of administrative workers the levels of damage were higher, usually significantly so, in the occupational groups. These comprised workers at a nuclear research reactor, a hospital diagnostic X-ray department, a coal mine and a mercury ore mine.

Human peripheral blood lymphocytes from 10 male donors were exposed to mitomycin C with and without prior irradiation with 0.01 Gy X-rays. Acute or chronic irradiation of lymphocytes in G1 resulted in a decrease in the subsequent level of mitomycin C-induced sister-chromatid exchange aberrations. The effect was small (approximately 10%) with evidence of some variability between donors. By contrast no adaptive response was observed if the cells were treated in G0.

An experiment sponsored by the International Atomic Energy Agency was undertaken to compare dose estimation by cytogenetic analysis on aliquots of samples of irradiated blood sent by air to participating laboratories. Accidental acute whole-body irradiations to 0.7 and 2.34 Gy and half-body irradiations to 3.5 Gy were simulated with X- and gamma-rays. For the partial irradiations the size of the irradiated fraction and its dose were estimated by the Qdr and contaminated Poisson techniques. Each laboratory's in vitro dose-response data were fitted to the quadratic model by the iteratively reweighted least squares method. Interlaboratory variations in dose-response curves, and in the aberration yields and dose estimates for the simulated accidents were noted. However, in general, most participants consistently obtained results acceptably close to the true values.

The Cytoscan 110 metaphase finder has been tested with cultures of human peripheral blood lymphocytes prior to its introduction into routine use for the analysis of radiation-induced chromosomal damage. Cells of varying quality and density of distribution on slides, stained with orcein or Giemsa, were examined by the same technician using the Cytoscan and a conventional microscope. The Cytoscan was able to locate rapidly (less than 2 min) virtually all metaphases known to be present and with an acceptably low rate of false positives. The presence of mixtures of FPG-stained first- and second-division spreads did not reduce its efficiency in metaphase finding. The instrument automatically divides the objects that it locates into 4 quality ranks and this was very effective in separating good metaphases, suitable for high-magnification scoring, from unscorable spreads and debris. With cultures of X-irradiated blood it was shown that the criteria by which the Cytoscan locates metaphases and ranks their appearance do not introduce bias in the yields of dicentric and other unstable chromosome-type aberrations.

Unstable chromosome aberrations induced by in vitro irradiation with zero plus seven low doses of 14.8 MeV D-T neutrons in the range 3.55-244 mGy have been analysed in human peripheral blood lymphocytes. In order to obtain the required large numbers of scored cells for such low doses, fourteen laboratories participated in the experiment. The dose responses for dicentrics, excess acentrics and total aberrations, fitted well to the Y = alpha D model. The alpha coefficient of yield for dicentrics, 1.60 +/- 0.07 X 10(-2) Gy-1, compares well with the values obtained in previous studies with D-T neutrons at somewhat higher doses. Results from a previous collaborative study using 250 kVp X-rays over a comparable dose range indicated the possible existence of a threshold below 50 mGy. In the present study there is no clear evidence for neutrons for such a threshold. However, the data were insufficient to permit the rejection of a possible threshold below approximately 10 mGy.

In vitro dose--response curves, for unstable chromosome aberration induction in human lymphocytes under conditions of full oxygenation or of anoxia, have been obtained using 250 kVp X-rays. Dicentric yields have been fitted to the quadratic function Y = alpha D + beta D2. An Oxygen Enhancement Ratio (OER) ranging from 7.2 to 2.7 was calculated from the coefficients of these curves possibly indicating that the data do not fit to the dose-modifying model of the oxygen effect although the differences are not statistically significant. A similar analysis of total aberration data yields an OER of 3.6 to 2.7 fitting much more satisfactorily to the dose-modifying model. Variations in dicentric yield induced by 3.0 Gy and 0.75 Gy of X-rays with increasing oxygen concentration were plotted and for each dose a constant dicentric yield was observed at oxygen levels of 2 and 250 ppm. Above 250 ppm yields increased steeply up to about 1% oxygen and then more gradually to a maximum at 100% oxygen.

Human peripheral blood lymphocytes from 20 donors were exposed in G0 to mitomycin C with and without prior acute irradiation with 0.01 Gy of 250 kVp X-rays. No evidence was found for the radiation having an hormetic effect on the level of sister-chromatid exchanges induced by mitomycin C.

An examination of the cytokinesis-blocked micronucleus technique confirmed its potential usefulness as a method of biological dosimetry for radiation accidents. Several advantages and disadvantages of the system are discussed. It has been demonstrated that under the conditions of these experiments, the blocking agent, cytochalasin B does not induce micronuclei or unstable chromosome aberrations. The induction of sister-chromatid exchanges proved just significant. Analysis of the dose response for 250 kVp X-rays indicates that although the Y = alpha D + beta D2 model fits the data, the relationship does not correspond to that for total aberration induction as might have been expected. The background frequency of micronuclei and the value of the alpha coefficient are higher than for total aberrations and the beta term is lower. This indicates that simple incorporation of acentric chromosome fragments into micronuclei may not wholly account for the phenomenon.