Chromosome aberrations in peripheral lymphocytes of patients irradiated with 15-MeV-photons for Morbus Hodgkin

Chromosome aberrations in peripheral lymphocytes of two Morbus Hodgkin patients were analyzed before and during the ongoing radiotherapy. Venous blood was taken 5 min after and before a successive irradiation in order to examine the dose dependence as well as the influence of mixed unirradiated and irradiated lymphocytes on the aberration rate. Both patients showed an overdispersed distribution of dicentric chromosomes and acentric fragment from the outset of therapy and independent of the time blood was taken. The dose-effect relationship established for both types of aberrations by the Maximum-Likelihood approach may best be described as being linear. The dose effect curves 5 min after a fraction did not differ from those calculated for a time thereafter. However, after the first two irradiations, the rate of dicentric chromosomes in the blood samples taken at a later time was about twice as high as that in the samples taken 5 min after irradiation. Dicentric chromosomes were twice more frequent during the entire radiotherapy than acentric fragments and about 30 times more frequent than centric ring chromosomes.     

Chromosome aberrations in mixed cultures of in vitro irradiated and unirradiated human lymphocytes

Human whole blood samples were exposed to different doses (1, 2, 4, 6 or 10 Gy) of gamma-radiation and mixed with different volumes of non-irradiated blood before culturing to simulate partial body irradiations. Chromosome aberrations were analysed and the frequency of dicentrics was found to be lower than expected, particularly when irradiated blood was mixed with large volumes of non-irradiated blood and after exposure to high radiation doses. For the mixtures of irradiated and unirradiated blood the deviation from the Poisson distribution depends on the respective proportions and on the doses. The results can be correlated to in vivo aberration frequencies in case of therapeutical treatments, but the yields of aberrations are generally underestimated in vitro.     

Chromosome aberrations in patients treated with telecobalt therapy for glioblastoma

The yield of dicentric chromosomes has been recorded in peripheral blood lymphocytes of patients undergoing telecobalt therapy for glioblastoma. Blood samples were taken by venipuncture, prior to the first radiotherapy session and 24 h after 10, 20 and 30 Gy to the tumor volume. On the basis of the maximum likelihood method, the yield of chromosome aberrations was best fitted by a linear quadratic dose-response relationship. According to this relationship, the dose inducing ten dicentrics at the target volume is 58 Gy, a value considerably higher than those found after radiotherapy for mammary carcinoma (15 Gy) or for pelvic tumors (5.62 Gy). Our results indicate that, in the case of fractionated exposures, confined to a small volume of the body, it is not possible to estimate the total dose administered and that the method only provides an estimate of the proportion of the lymphocytes irradiated.     

Chromosome aberrations in Crepis capillaris after gamma-irradiation and clinostatism

The rate of cell division and emergence of spontaneous and radiation chromosomal aberrations in Crepis capillaris exposed to clinostating were determined. The plants were gamma-irradiated with 300 R during clinostating when the primary roots were 1-2 mm long. The velocity of clinostat rotation was 2 rpm. The mitotic index was not affected either by clinostating alone or combined with irradiation. The exposure to clinostating did not change significantly the total frequency of nuclear aberrations or the distribution of the aberrations of the chromosomal and chromatin type as well as aberrations resulting from one or two radiation events. Thus, the effect of clinostating combined with gamma-irradiation can be considered zero.     

Follow-up of stable chromosomal aberrations in gamma-ray irradiated non-human primates

PURPOSE: The purpose of this study was to examine a new approach to retrospective biological dosimetry, by using a long-term animal model to determine the stability of translocation frequency after in vivo irradiation. While the frequency of dicentrics is known to decrease over time, the persistence of more stable chromosomal aberrations such as translocations could be useful if their stability were definitively proved. MATERIALS AND METHODS: Four monkeys (Macaca fascicularis) were exposed to two different doses of ionizing radiation: 2 Gy whole body irradiation for two and 4 Gy for two others. Blood samples were obtained at various times after irradiation. Both total and two-way translocations were detected by fluorescence in situ hybridization. Translocations were scored in stable cells, that is, those without dicentrics, rings or fragments. The course of translocation frequency was analysed at four time-points: one hour (H1), 2 months (M2), 10 months (M10) and 31 months (M31) after irradiation. RESULTS: We observed two separate trends in translocation frequency: Total translocation frequency decreased slightly in animals irradiated with a dose of 2 Gy, while two-way translocation frequency was relatively stable in all irradiated animals. CONCLUSIONS: We confirmed the long-term stability of translocations and found that it seems to depend on the type of the translocation recorded. Overall translocations were stable for up to 31 months regardless of dose, but two-way translocations were more stable than those that were non-reciprocal, especially in stable cells.     

Chromosome aberrations induced in human lymphocytes by 16.5 MeV protons

In a track segment irradiation experiment with 16.5 MeV protons the induction of dicentrics was studied in human T-lymphocytes. The dose-response relationship was linear quadratic with estimated parameters alpha = (0.44 +/- 0.07) x 10(-1) Gy-1 and beta = (1.95 +/- 0.30) x 10(-2) Gy-2. With respect to X-rays a limiting RBE of 1.1-1.2 exists. The present findings are compared with data from other laboratories obtained with 4.9 and 8.7 MeV protons. It was found that the data do not fit theoretical predictions on a proportional relationship between alpha values and LET. Using the microdosimetric quantity yD (25 nm), the dose average of the lineal energy, for characterization of these proton radiations, at a relevant site diameter of 25 nm the ratio of yD = 1.15 is in accordance only with the observed alpha ratio of 1.0 +/- 0.23 for 8.7 and 16.5 MeV protons. In contrast to the prediction of a constant beta at low LET values, the quadratic coefficients increase with increasing LET between 3 and 8 keV/microns.     

Urothelial renal pelvic tumours in phenacetin abusers.

The appearances of renal pelvic tumours at urography and pyelography in 25 phenacetin abusers were correlated with the microscopy of operative specimens. Radiography was found to contribute to the preoperative assessment of malignancy grade.     

Chromosome aberrations induced in human lymphocytes by U-235 fission neutrons

Aim

Further experiments were performed to explain a difference in chromosomal aberration yield found between samples cultivated immediately after fission neutron irradiation and samples which were cultivated with 96 h delay after irradiation.

Material and Method

Human peripheral blood samples were irradiated in mixed fission neutron/gamma field (1800 s) and biological effect assessed in the mean of analysis of unstable chromosome aberrations with a time delay in culturing cells of 12, 24, 48, and 96 h. Additional measurements were performed on irradiated and blank blood samples with the aim to detect any increase in α and β activity after fission neutron irradiation. No difference was found. Results were compared to theoretically calculated values of the α and β activity released from natural radioactive isotopes.

Result and Conclusion

As a conclusion it is shown that in our experimental conditions the secondary effects resulting from nuclear transformations of natural or induced radioactive isotopes, recoil reactions and accompanying α, β, and γ radiation are not the reason for the increase observed in chromosomal aberration yield in blood samples cultured with a time delay of at least 24 hours.     

Repair inhibition in tumours irradiated with fast protons and negative pions

Solid Ehrlich mouse tumours were irradiated in the 80 MeV proton beam of the Paul-Scherrer-Institute. The tumour volume was measured as a function of time after irradiation and two experimental endpoints were determined: local tumour control and minimal tumour volume after irradiation. The application of 2-deoxy-D-glucose (2-DG; 2 mg/kg) increased the radiation effect of protons by a factor of 1.4. The same tumour system was used with negative pions. Human tumours are usually irradiated with a mixed radiation produced by the "spot-scan-technique". This radiation quality was simulated in the mouse experiment by two successive irradiations with a spot of densely ionizing peak pions and a spot of sparsely ionizing plateau pions. Application of 2-DG raised the radiation effect due to the sparsely ionizing component again by a factor of 1.4. This indicates that clinical results in radiotherapy might be improved by application of 2-DG during the treatment.     

Cell survival and chromosomal aberrations in CHO-K1 cells irradiated by carbon ions

Chinese hamster ovary CHO-K1 cells were exposed to high LET ¹²C-beam (LET: 830 keV/μm) in the dose range of 0–6 Gy and to ⁶⁰Co irradiation and the RBE value was obtained. Effects of ¹²C-beam exposure on cell survival and chromosomal aberrations were calculated. The chromosomal aberration data were fitted with linear equation. The distribution of aberration in cells was examined with a standard u-test and used to evaluate the data according to Poisson probabilities. The variance to the mean ratio σ²/Y and the dispersion index (u) were determined. Overdispersion was significant (p<0.05) when the value of u exceeded 1.96.     

Salivary scintigraphy for assessing the protective effect of pilocarpine in head and neck irradiated tumours

Patients with head and neck cancers can develop salivary hypofunction after radiotherapy. The use of pilocarpine during radiotherapy treatment has been shown to be an effective treatment, although its usefulness is being discussed. The aim of this study was: (1) to determine the value of a semiquantitative scintigraphy method for measuring the uptake and excretory salivary function of patients with head and neck irradiated tumours; and (2) to study the usefulness of pilocarpine as a salivary gland protector during radiotherapy. We prospectively studied 49 patients (mean age 61 years, range 29-87 years) with head and neck cancer in need of radiotherapy. Patients were divided into two groups consecutively: group P (26 patients) received 5 mg of pilocarpine three times per day starting the day before radiation therapy, and group NP (23 patients) received radiotherapy without pilocarpine and were used as the control group. Salivary gland scintigraphy and a visual analogue scale (VAS) of mouth dryness were obtained from each patient before radiotherapy and during the first year after treatment. The most frequent finding after radiotherapy was a quick impairment in parotid and submaxillary excretion (P < 0.001). There were no statistical differences comparing the pilocarpine group against the non-pilocarpine group. Parotid and submaxillary uptake significantly decreased after radiotherapy in both groups (P < 0.001). However, a tendency to recover within the pilocarpine group was observed in both the parotids and the submaxillary glands at 12 months. No differences were found comparing the VAS results in both groups. Strikingly, VAS data did not correlate with salivary gland dysfunction observed by means of scintigraphy. In conclusion, salivary scintigraphy is a useful technique to evaluate objectively the salivary gland function of patients with head and neck irradiated tumours as well as to test the response to pilocarpine. However, despite better results on the salivary uptake at 12 months, pilocarpine did not significantly improve salivary gland function.