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The induction of chromosome aberrations by low LET radiations was studied in peripheral lymphocytes and spermatogonial stem cells of the male marmoset. The data showed that there was not significant difference in the sensitivity of the lymphocytes whether they were irradiated in vitro or in vivo, but the frequency of heritable translocations recovered in the primary spermatocytes were considerably lower than that calculated to occur in the lymphocytes. The data are used to make estimates of human genetic risk from radiation based on limited interspecific comparisons.

In order to assess the potential of cytogenetic determinations on peripheral blood lymphocytes as a means of monitoring human populations subject to low level occupational and environmental exposures to chemical mutagens and carcinogens, accurate baseline data are required. Accordingly, we have determined mean frequencies of chromosomal aberrations and of sister-chromatid exchanges, their variances, and the sources of this variance in a cohort of 353 healthy employees of the Brookhaven National Laboratory. A detailed protocol was adopted for blood sampling, lymphocyte culture, cytogenetic preparation and scoring in order to minimize variation from these potential sources. Scoring was divided between the Oak Ridge and the Brookhaven groups with duplicate scoring sufficient to evaluate and minimize the effect of any differences between laboratories or between individual scorers. In all, the data include 71,950 cells scored for chromosomal aberrations and 16,898 cells scored for sister-chromatid exchanges. The mean unadjusted frequency of sister-chromatid exchanges was 8.29 +/- 0.08/cell. As reported in other studies, cigarette smoking very significantly influenced sister-chromatid exchange frequencies; in our study the mean for smokers was 9.0 +/- 0.2, while that for non-smokers was 8.1 +/- 0.1/cell. The mean frequency was statistically higher in females than in males, regardless of smoking status. On the other hand, age of the subject did not significantly influence sister-chromatid exchange frequencies. Curiously, the subject's total white cell count did influence sister-chromatid exchange frequency. No other source of variation was found. The frequencies of chromosomal aberrations of all types were determined. The frequency of the most common unequivocal chromatid type, the chromatid deletion, was 0.81 +/- 0.05%, that of the most common unequivocal chromosome type, the dicentric, was 0.16 +/- 0.02%. No statistically significant influence was found of age or sex, nor of any other parameter tested, on the frequency of any chromosomal aberration type, with the single exception of long acentric fragments, often "supernumerary", believed to represent X chromosomes precociously separated at the centromere. Such fragments were significantly more frequent in samples from females than those from males, and showed a significant positive regression on age.

The thymidine (dThd) analog 5-bromodeoxyuridine (BrdUrd) is widely used in studies of the induction of sister chromatid exchanges (SCEs), since growth in the presence of BrdUrd allows the subsequent differential staining of the chromosomes through the fluorescence-plus-Giemsa (FPG) method. However, the analog itself induces SCEs, an aspect of its use which is often not considered. We have studied the induction of SCE by BrdUrd and a second dThd analog 5-chlorodeoxyuridine (CldUrd). Growth of Chinese hamster ovary (CHO) cells for 2 rounds of replication in the presence of different concentrations of either analog results in increasing results in increasing SCE frequencies which are linearly proportional to the degree of analog substitution for dThd in the DNA. However, CldUrd causes 3 to 5 times the number of SCEs found with BrdUrd, at equivalent substitution for dThd. With both analogs the increase in SCE frequency is due to the replication of the analog-substituted DNA and not to the incorporation of analog into nascent DNA. This induction of SCE can be considered at the level of a single strand of DNA since the replication of bifilarly substituted DNA results in twice the number of SCEs that are induced by the replication of unifilarly substituted DNA.

Cell line ML-1 was established from a myelogenous leukemia of an RFM mouse. The ML-1 cells and in vitro normal mouse bone marrow cells were analyzed to determine if there was a differential sensitivity to X-ray-induced chromosome aberrations in G1 cells and/or differences in postirradiation cell cycle progression. Cells identified as being in G1 at the time of irradiation by their staining pattern after replication in 5-bromodeoxyuridine were analyzed for all types of chromosomal aberrations following X-ray doses of 0.5, 1.0, 1.5, and 2.0 Gy. ML-1 cells showed a greater sensitivity to the induction of both chromosome-type aberrations (dicentrics and terminal deletions) and chromatid-type aberrations (exchanges and deletions) compared to normal mouse bone marrow cells, which only contained chromosome-type aberrations. The presence of chromatid-type aberrations in the ML-1 cells and not normal bone marrow cells suggested a differential progression through the cell cycle for the two cell types after irradiation. Mitotic index and flow cytometric analyses were performed and showed that both cell types have a delay in progression from G2 into mitosis, but only the normal mouse bone marrow cells have a delay in progression from G1 into S, as well as delayed progression through the S phase following X-irradiation. These results indicate that the ML-1 leukemia cells have an increased radiosensitivity. This may be due to a defect in their ability to respond to DNA damage as evidenced by their lack of a G1- and S-phase delay which allows normal cells an increased time to repair DNA damage before replication. These same characteristics have been observed in ataxia telangiectasia cells and may well represent a general feature of cells with increased radiosensitivity.

This report presents an assessment made by the U.S. Environmental Protection Agency Gene-Tox Program's Work Group on mammalian cytogenetics of the clastogenic effects of chemicals in in vivo and in vitro mammalian cell assays. This assessment is based on information provided by the Environmental Mutagen Information Center, Oak Ridge National Laboratory, with the proviso that the experimental protocol used in these papers was adjudged to be acceptable by standards outlined by the Work Group. Some data were accepted as "qualitative only" because the protocol used was fairly close to that proposed as suitable. Using these criteria, 177 papers were selected for review. 6 assays were reviewed: bone marrow (32 papers, 31 chemicals), spermatogonial (10 papers, 10 chemicals), spermatocyte (25 papers, 25 chemicals), oocyte or early embryo (18 papers, 19 chemicals), in vitro cell culture (30 papers, 66 chemicals), and leukocyte (66 papers, 53 chemicals). Each assay was considered separately, and comparisons were then made between them for their similarities or differences in producing a positive or negative clastogenic effect of a particular chemical or chemical class. A large proportion of the available cytogenetic data was not suitable for inclusion in the final data base because of poor experimental design or unsatisfactory reporting of the information. It was not possible to recommend any one assay for determining potential clastogenicity because each had its own particular advantages and limitations and provided unique information. For demonstrating in vivo effects, the bone-marrow assay is probably the simplest and most economical. If only in vitro exposures were considered, leukocytes or cultured mammalian cell lines would be suitable. However, there are advantages to using leukocytes because they are a synchronous population, at least through their cell division, and because of the ready availability of human cells. In general, there was good agreement between clastogenicity and carcinogenicity.

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The induction of myeloid leukemia following fission neutron irradiation was examined over the 0-80 rad dose range. Over this dose range the dose response could be described by the linear regression equation: y = 0.94 + 0.18X. A comparison of these data with data obtained following gamma irradiation from this study and a previous study indicated that the relative biological effectiveness for myeloid leukemia induction was 2.8. These results appear to be compatible with those reported by other investigators.

The yield of chromosome aberrations was followed for a period of 2 yr following whole-body irradiation of marmosets, and for 3 yr following an accidental whole-body exposure of a human. The yield of dicentrics plus rings decreased significantly 1 wk after irradiation of marmosets, but did not change in man until 5 wk after exposure. The yield of dicentrics and rings in the human has remained relatively constant for 3 yr, at one-half that immediately after irradiation. In the marmosets, a further decrease in yield was observed at 30 wk following 300 R and at 45 wk following 100 R, so that the yield was around 2%, compared with 40% immediately after 200 R and 15% immediately following 100 R. The yield remained at this low level through 90 wk after exposure. These differences in the persistence of aberrations in marmoset and man are considered both in terms of the different patterns of lymphocyte recovery in the two species following irradiation, and in terms of differences in lymphocyte turnover rate and li...

Chromosome aberration yields were obtained from short-term peripheral leukocyte cultures established at various times after an accidental whole-body exposure to60 Co γ-rays. The yield of centric rings plus dicentrics did not vary significantly over the first 32 days after exposure. The mean yield for this sampling period was 0.228 ± 0.010 centric rings plus dicentrics per cell. Based on the coefficients of aberration production obtained from an acute γ-ray dose-response study on cells in vitro this yield corresponds to an average midline dose of 144 R. This biological estimate is in excellent agreement with the physically derived estimate of 127 R that was obtained by irradiating an Alderson Rando phantom containing LiF thermoluminescent dosimeters under conditions as similar as possible to those of the patient's exposure.