Analysis of α-particle-induced chromosomal aberrations by chemically-induced PCC. Elaboration of dose-effect curves

Abstract

In a similar way to high-dose exposures to low-LET radiations, cells show difficulties reaching mitosis after high-LET radiation exposure. For this reason, techniques have been proposed that are able to analyze chromosome aberrations in interphase by prematurely condensing the chromosomes (PCC-techniques). Few dose-effect curves for high-LET radiation types have been reported, and none for α-particles. The aim of this study was to evaluate, by chemically-induced PCC, the chromosome aberrations induced by several doses of α-particles. Monolayers of peripheral lymphocytes were exposed to an α-source of Americium-241 with a mean energy entering the cells of 2.7 MeV. Lymphocytes were exposed to 10 doses, from 0-2.5 Gy, and then cultured for 48 h. Colcemid and Calyculin-A were added at 24 and 1 h before harvesting, respectively. During microscope analysis, chromosome rings and extra chromosome pieces were scored in G2/M-PCC and M cells, while dicentric chromosomes were only scored in M cells. As the dose increased, fewer cells were able to reach mitosis and the proportion of G2/M-PCC cells increased. Chromosome rings were hardly observed in M cells when compared to G2/M-PCC cells. Extra fragments were more frequent than rings in both G2/M-PCC and M cells, but with lower frequencies than in G2/M-PCC cells. The distribution of dicentrics and extra fragments showed a clear overdispersion; this was not so evident for rings. The dose-effect curves obtained fitted very well to a linear model. Damaged cells after α-particle irradiation show more difficulties in reaching mitosis than cells exposed to γ-rays. After α-particle irradiation the frequency of all the chromosome aberrations considered increased linearly with the dose, and α-particles clearly produced more dicentrics and extra chromosome pieces with respect to γ-rays. After α-particle exposure, the existence of extra chromosome fragments in PCC cells seems to be a good candidate for use as a biomarker for dose assessment. However, the observed frequencies of different types of chromosomal aberrations could be influenced by some methodological aspects; for this reason, and in order to avoid possible methodological bias, standardization of the technique will be desirable.

The role of dosimetry and biological effects in metastatic castration–resistant prostate cancer (mCRPC) patients treated with 223Ra: first in human study

“…The number of DC and MN observed in the PBLs has been plotted against the AD to blood. A linear correlation (increase) has been found between AD to blood and DC number as reported for other radionuclides [ 11 , 18 , 31 ].…”

Investigation of DNA Damage and Cell-Cycle Distribution in Human Peripheral Blood Lymphocytes under Exposure to High Doses of Proton Radiotherapy

“…The same received dose may result in dissimilar cytotoxic and genotoxic effects. Observed differences in response to various types of radiation may result from many patient factors [33]. The genetic component is significant for individual radiosensitivity; however, environmental factors, lifestyle, diet, physical activity, and hormonal status also influence the observed effects [8,34].…”

Dose Response Curve Using Chemically Induced PCC Assay in Peripheral Cells Irradiated In-vitro to 5 MeV Alpha Particles Emitted From Radon Source

“…In the present study, over dispersion of dicentrics was observed beyond 4.6 mGy. Puig et al [12] showed an initial increase in dicentric distribution with over dispersion for 0.05 Gy, 0.1 Gy and there was decline till 2.5 Gy. Many other authors had similar observation in the over dispersion [13,16].…”

“…There are many reports on dose response curve for low LET radiation [8][9][10] and for high-LET radiation using PCC assay [8,11] and none of them for alpha particles. However, there is one recent report about the dose response for α-particles with the maximum dose of 2.5 Gy [12]. But till date no report exists for dose response curve of radon using PCC technique.…”