Geno- and cytotoxic effects in bone marrow cells and peripheral blood induced by the prolonged administration of 131I to the laboratory rats. / GENO- TA TsYTOTOKSYChNI EFEKTY V KLITYNAKh KISTKOVOGO MOZKU TA PERYFERYChNOI KROVI, INDUKOVANI TRYVALYM NADKhODZhENNIaM RADIOIZOTOPU 131I DO ORGANIZMU LABORATORNYKh ShchURIV.

OBJECTIVE: to evaluate the state of to assess the state of hematopoietic system of experimental rats according to the geno and cytotoxic effects in bone marrow and changes in morphology composition of peripheral blood caused by prolonged 131I intake. MATERIALS AND METHODS: Within 15 days sodium iodide with activity of 29,3 kBq/animal was daily orally administered to Wistar rats. At 1, 2, 3, 7 and 15 days specific radioisotope activity, level of micronuclei in bone marrow cells, cyto toxicity index, number of erythrocytes and leucocytes in peripheral blood were determined. RESULTS: It is established that the maximum genotoxic effect induced by 131I prolonged intake was formed at the early terms of observations followed by the reduction of cytogenetic damage in bone marrow cells of rats, while the cytotoxic effect of 131I was formed at the remote terms of administration. Changes in peripheral blood morphology were caused by left shift leukocytosis due to immature forms of neutrophils. In leucograms throughout the experi ment increased levels of lymphocyte atypical forms were observed. CONCLUSION: Prolonged administration of 131I to the laboratory rats does not cause dose dependent changes of cyto and genotoxic markers in the bone marrow and peripheral blood cells.

Fractionated low-dose radiation exposure potentiates proliferation of implanted tumor cells.

AIM: The purpose of this study is to test whether whole-body fractionated exposure of tumor-free animals to low doses of low-LET radiation (at the total delivered dose of 1.0 Gy of X-rays) is capable of potentiating growth of subsequently implanted tumor cells. MATERIALS AND METHODS: Adult male rats were fractionally exposed to low doses of X-rays (10 acute exposures with 0.1 Gy each and with a frequency of 1 exposure per 3 days). The next day after the last irradiation rats were implanted with Guerin carcinoma (GC) cells. On the 12th and 18th days after implantation of GC cells, animals were sacrificed, and the mass of tumors was measured by weighing them, although the kinetics of tumor growth was also examined by daily measurements of the dimensions of tumors. Cytotoxic effects in the bone marrow were assessed flow cytometrically in acridine orange-stained unfractionated bone marrow cells using the ratio of polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE). RESULTS: In irradiated rats, tumors grew apparently faster than in unirradiated rats for up to 18 days after implantation of GC cells. On the 18th day after implantation of GC cells the average value of the mass of tumors in irradiated rats was 2.8-fold higher compared with the average value of the mass of tumors in unirradiated rats (p < 0.05). On this day post-implantation, the bone marrow in irradiated animals was 1.8-fold more suppressed (as evidenced by decreased PCE/NCE ratios) than that in animals that were irradiated, but were not implanted with GC cells (p > 0.05), and was 1.4-fold more suppressed than that in animals that were not irradiated, but were implanted with GC cells (p > 0.05). CONCLUSION: Fractionated irradiation of tumor-free animals with low doses of X-rays potentiates proliferation of subsequently implanted GC cells. This potentiation seems to be associated with radiation-induced impaired hematopoiesis.

Chromosomal radiosensitivity in Ukrainian breast cancer patients and healthy individuals.

AIM: Recent studies showed that increased chromosomal damage induced by ionizing radiation is observed among patients with different tumor types. The aim of the study was evaluation of chromosomal radiosensitivity in breast cancer (BC) patients (n = 37) and healthy women (n = 44). METHODS: Chromosomal radiosensitivity was assessed with G0 and G2 assay. For G0 assay lymphocytes were exposed in vitro to 1,5 Gy of X-rays before culture setting. For G2 assay lymphocytes were irradiated with 0,5 Gy of X-rays after 47 h of incubation. RESULTS: Significant differences in mean scores both of G0 and G2 assay between breast cancer patients and controls were observed indicating the increased chromosomal radiosensitivity of lymphocytes of cancer patients. 11% of healthy women and 38% of BC patients were determined to be radiosensitive with G2 assay. CONCLUSION: Obtained results support the concept of association between elevated individual G2 chromosomal radiosensitivity and predisposition to BC.

The long-range cytotoxic effect in tumor-bearing animals.

AIM: The relationship between cancer and patient health is still of great interest for experimental and clinical oncology. The tumor can adversely affect surrounding and distant tissues as well. However, effects of the tumor on distant tissues are much less studied than its effects on surrounding tissues. This study was aimed to test whether the tumor could trigger cytotoxic and/or genotoxic signals with respect to the distant proliferative tissue such as bone marrow. MATERIALS AND METHODS: Rats were subcutaneously implanted with Guerin carcinoma cells, and on the 12(th) and 18(th) days after implantation both cytotoxic and genotoxic effects were assessed by flow cytometry in acridine orange stained unfractionated bone marrow cells isolated from femur. The cytotoxic effect was assessed using ratios of the following cell populations: total nucleated cells (TNC)/total enucleated erythrocytes (TE); polychromatic erythrocytes (PCE)/normochromatic erythrocytes (NCE). The genotoxic effect was assessed by quantification of micronucleated PCE (MNPCE) within the population of PCE. RESULTS: A significant cytotoxic effect was observed in tumor-bearing animals on the 12(th) and 18(th) days after implantation (≈ 2-fold decrease in both TNC/TE and PCE/NCE ratios compared with corresponding parameters in control animals). There was also a genotoxic effect in these animals (a slight increase in the number of MNPCE), however, this effect was insignificant. The PCE/NCE ratio reversely correlated with the tumor weight which is suggestive of the link between erythropoietic cytotoxicity and tumor progression. CONCLUSION: Cytotoxic insult to the bone marrow is likely to be associated with the mechanism(s) triggered by distantly located tumors whose growth may correlate with the cytotoxic effect.

Increased individual chromosomal radiosensitivity of human lymphocytes as a parameter of cancer risk.

AIM: Evaluation of chromosomal radiosensitivity of healthy individuals and determination those with the increased susceptibility to radiogenic cancer. METHODS: Cytogenetic examination of radiation induced injuries in lymphocytes of healthy individuals (n=103) was carried out on the basis of G(2)-assay. Test system of peripheral blood lymphocytes with metaphase analysis was used. RESULTS: On the basis of the obtained "stage-effect" and "dose-effect" calibrating curves the scheme of cytogenetic examinations of healthy individuals was developed. Analysis of cytogenetic parameters induced by G(2) irradiation at 1.5 Gy dose revealed their high interindividual variability. The highest differences were registered for chromatid type aberrations (CV=42.1%) with the chromatid break predominance in the spectrum (CV=37.5%). Statistical analysis of the distributions of the obtained individual cytogenetic parameters indicated 12% individuals with increased chromosomal radiosensitivity. CONCLUSIONS: Cytogenetic evaluation of individual chromosomal radiosensitivity based on G(2)-assay has its perspectives in the formation of groups with increased risk of radiogenic cancer developing and its primary prophylactics among healthy population.