Irradiated Human Lymphocytes Research Articles

DNA Content of Micronuclei in Human Lymphocytes

We have calculated the distribution of DNA contents in micronuclei (MN) induced by ionizing radiation in human lymphocytes on two assumptions: the MN arise from acentric chromosome fragments (ACF), and the ACF result from the random breakage and rejoining of chromosomes. Measurements show that about 80 per cent of MN have a DNA content in the range of 0.5-6 per cent of the G1 nucleus. This group is consistent with the model and shows little dependence on radiation dose over the dose range of 0.5-4 Gy, or on lymphocyte culture time, varying from 48 to 76 hours. The MN with DNA content from 6 to 20 per cent of the G1 nucleus are probably the result both of spindle defects and of DNA synthesis in MN.

Kinetics of the effect of ara C on chromosome aberration yield in irradiated human lymphocytes.

In unstimulated lymphocytes the enhancing effect of ara C on the yield of X-ray-induced dicentric aberrations was maximal if ara C was added immediately or up to 2 h after irradiation. When ara C was added later the enhancing effect decreased and practically vanished by 5 h. In stimulated lymphocytes the ara C effect declined faster and practically vanished by 3 h. If ara C was added for 1 h immediately after irradiation, then the aberration yield observed in G0, early G1 and late G1 cells was similar whereas it increased significantly from G0 to late G1 cells without ara C post-treatment. The results are discussed in relation to the classical model of aberration formation.

Effect of L-cysteine on the dose-effect relationship for chromosome aberrations in irradiated human lymphocytes.

Effect of L-cysteine on the dose-effect relationship for chromosome aberrations in irradiated human lymphocytes.

Chromosome Dosimetry: The Influence of Culture Media on the Proliferation of Irradiated and Unirradiated Human Lymphocytes

Chromosome Dosimetry: The Influence of Culture Media on the Proliferation of Irradiated and Unirradiated Human Lymphocytes

Inhibitors of poly(ADP-ribose) polymerase enhance unscheduled DNA synthesis in human peripheral lymphocytes

Benzamide and m -aminobenzamide, the most potent inhibitors of poly-(adenosine diphosphate ribose) polymerase known, enhanced unscheduled DNA synthesis after ultraviolet irradiation in human lymphocytes. A positive correlation was found between the inhibitory activities and enhancing effects on unscheduled DNA synthesis of inhibitors related to benzamide and nicotinamide. Lymphocytes of a patient with xeroderma pigmentosum did not show enhanced unscheduled DNA synthesis with these inhibitors after ultraviolet irradiation, but like normal lymphocytes, showed enhanced unscheduled DNA synthesis after treatment with N-methyl-N′-nitro-N-nitrosoguanidine.

Stimulation of irradiated human lymphocytes by different mitogens.

Stimulation of irradiated human lymphocytes by different mitogens.

The radiosensitivity of chromosomes of rabbit lymphocytes

Dicentrics were induced in human and rabbit lymphocytes in vitro by exposure to X-irradiation. The yields were compared with data reported in the literature. To elucidate the reasons for the different findings we have evaluated the parameters for the different models by maximum likelihood methods. From this analysis it can be concluded that the earlier claim of Bajerska and Liniecki [1] that both species have the same radiosensitivity must be discounted, and that their similarity was due to the abnormally low values these investigators observed in irradiated human lymphocytes.

The RBE of 30 kV X-rays for the induction of dicentric chromosomes in human lymphocytes.

The frequency of dicentric chromosomes induced by the irradiation of human lymphocytes in Go phase was determined with hard (150 kV) and soft (30 kV) X-rays. When a linear-quadratic dose-effect relation was used to fit the experimental data, a significant linear contribution was found for 30 kV X-rays. The RBE of 30 kV compared with 150 kV X-rays approaches the value 3 at a 30 kV X-rays dose of 20 rad and decreases with increasing dose. From the results it may be concluded that chromatids with primary breaks, undergoing second order reactions and thus forming dicentric chromosomes, are produced by traversals of low-energy electrons through chromatin material.

Association of centrioles and chromosomes observed in preparations of whole-mounted human chromosomes.

Pairs of centrioles are a frequent finding in whole-mounted, critical-point-dried chromosome preparations from normal and irradiated human lymphocyte cultures. Most frequently they are found in association with a group C chromosome, although apparently free diplosomes are not uncommon. Fibers that in every respect are the morphologic equivalent of those seen in the body of the chromatid connect to the thick-walled open-ended part of the parent centriole. These features argue for the possibility that fibers connecting centrioles are an integral part of nuclear or chromosomal chromatin. It was observed that the smaller (daughter) centriole was connected and held in the well-known angular configuration to the thick-walled opne end of the parent centriole by a few, probably only two, colchine-resistant fibers.

The Sites of Unscheduled DNA Synthesis within Irradiated Human Lymphocytes

The sites of unscheduled DNA synthesis (UDS) induced by ultraviolet or ionizing radiations in human lymphocytes are not randomly distributed in the nuclear DNA. Examinations of radioautographs of 1.0-μm nuclear sections show that about 70% of the grains are over the 33% of the nuclear area adjacent to the nuclear membrane. This is found whether the bulk of the DNA, which is in heterochromatin masses, is peripherally distributed, is dispersed throughout the nucleus, or is homogeneously distributed. This peripheral distribution of UDS is maintained when incubation time is increased from 0.5 to 4 hr, and when cells are stimulated for 18 hr by phytohemagglutinin prior to irradiation. The distribution of UDS sites is not simply related to the distribution of euchromatin (active) or heterochromatin (repressed) within the nucleus.

Do one-hit chromosome exchanges exist? Dose-response relation for irradiated human lymphocytes.

It is demonstrated that the expectation of a quadratic dose-response relation for two-hit aberrations is not correct. In fact the theoretical curve is changed from near-quadratic to near-linear when the dose increases and fits well the experimental data on production of exchanges in human lymphocytes by radiation. The commonly used relation y = alphaD + betaD2 shows systematic deviations from the observed frequencies. Therefore, no reason exists to postulate some fraction of exchanges to be produced by a one-hit mechanism.

Letter: The lymphocyte response to phytohaemagglutinin after in vitro irradiation.

Braeman and Moore (1974) reported the response of irradiated human lymphocytes to phytohaemagglutinin (PHA). Their observation of the marked effect of irradiation on the morphological transformation of lymphocytes differs rather considerably from that of a number of studies hitherto reported. While the dose-effect curve of Braeman and Moore (1974) shows that irradiation of blood in vitro with 200 rads and 800 rads suppressed the transformation of lymphocytes by about 40 and 75 per cent respectively, Sato and Sakka (1970) reported that irradiation of human lymphocytes in vitro with 300 R did not exert any effect and that irradiation with 2,000 R caused a decrease in transformation of only 40 per cent. Conrad (1969) reported similar findings that in vitro irradiation of human lymphocytes with doses up to 300 R caused no effect and 1,000 R induced only 20 per cent depression in the ability of lymphocytes to transform upon a stimulation by PHA. The lack of significant decline in PHA response of blood lymphocytes following in vitro irradiation has also been demonstrated by Schrek and Stefani (1964).

Interaction distance of primary lesions in the formation of dicentric chromosomes after irradiation of human lymphocytes with 3-MeV electrons in vitro

The rejoining distance for the formation of dicentric chromosomes in human lymphocytes is derived on the basis of microdosimetric concepts. For the formation of a dicentric chromosome, primary lesions produced by absorption events can interact within the nucleus over a distance of between 0.5 and 1.0 μ. The intercellular distribution of dicentric chromosomes is consistent with a Poisson distribution.

Application of Chromosome Aberration Frequency in Human Lymphocytes to Biological Dosimetry

This is a brief investigation of biological dosimetry for human subjects. During the past decade techniques have been developed for the analysis of radiation-induced chromosome aberrations in human lymphocytes. As a result, a vast amount of studies on chromosome aberrations induced by radiation in human lymphocytes have been carried out. These studies have revealed the relationships between aberration frequencies and absorbed doses. At present this method appears to be the most readily quantifiable one of biological dosimetry available.The problems associated with the use of this method in estimating radiation dose are discussed. These problems include time of sampling after irradiation, culture time, dose rate, type of radiation, temperature at the time of irradiation, etc.

Noninvolvement of the human X chromosome in X-ray induced exchanges.

The patterns of breaks and exchanges induced by X irradiation of human lymphocytes obtained from individuals with abnormal sex-chromosome complements have been analyzed and compared with similarly induced aberrations in cells from normal individuals. Statistical analysis showed that the X chromosome(s) showed a different pattern of response to X irradiation than did the autosomes. Neither the active nor the inactive X behaved like the autosomes in this respect.

Kinetics of Unscheduled DNA Synthesis Induced by Ionizing Radiation in Human Lymphocytes

A study of the rates of incorporation of3 H-thymidine ( ${}^{3}{\rm HTdR}$ ) and ${}^{3}{\rm H}\text{-deoxycytydine}$ ( ${}^{3}{\rm HCdR}$ ) into the DNA of human lymphocytes following exposure to ionizing radiation suggests the presence of two processes: One is rapid, essentially completed within an hour after irradiation; the other is slow and persists for at least 7 hours after irradiation. The rapid process can be adequately represented by a simple enzyme model for which the substrates are ${}^{3}{\rm HTdR}$ or ${}^{3}{\rm HCdR}$ and the radiation-induced lesions in the DNA. In terms of the model, the effect of anoxia is to decrease two-fold the concentration of lesions. The action of phytohemagglutinin is to double the concentration of enzyme prior to the onset of normal DNA synthesis. The slow process can also be represented by a simple enzyme model with radiation-induced lesions as substrate.