[en] To determine whether in the lymphocyte the frequency of chromosome aberrations might be influenced by a differential radiation response of the varying types of cells, as well as interactions among them, subpopulations were separated on the basis of differences in cell surface receptors. The subpopulations, namely, T and B lymphocytes and three T subsets, T-M, T-G, T-null, were found to differ in radiosensitivity as measured by survival in culture and mitotic index after PHA stimulation. All the populations studied are represented to varying degrees among the mitotic cells of unirradiated samples 48 hours after PHA stimulation. At increasing doses of ⁶Co gamma rays (50, 100, 250, 500 rads), however, their proportions change both as a direct result of irradiation, such as cell killing, and as an indirect effect, such as the reduction in suppressor cell action

[en] The polyamine spermine and the disulfide N,N double-prime-(dithiodi-2,1-ethanediyl)bis-1,3-propanediamine (WR-33278) are structurally similar agents capable of binding to DNA. WR-33278 is the disulfide moiety of the clinically studied radioprotective agent S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721). Because of their reported structural and functional similarities, it was of interest to characterize and compare their radioprotective properties using the endpoints of cell survival and mutation induction at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in Chinese hamster AA8 cells. In order to facilitate both the uptake of WR-33278 into cells and the direct comparison between the protective properties of WR-33278 and spermine, these agents (at concentrations of 0.01 mM and 0.001 mM) were electroporated into cells. The exposure of cells to both electroporation and irradiation gave rise to enhanced cell killing and mutation induction, with the sequence of irradiation followed 3 h later by electroporation being the more toxic protocol. Enhanced cell survival was observed following electroporation of 0.01 mM of spermine and WR-33278 30 min prior to irradiation; protection factors (PF) of 1.3 and 1.8, respectively. Neither agent was protective at a concentration of 0.001 mM. Protection against radiation-induced hprt mutations was observed for both spermine and WR-33278 under all experimental conditions tested. These data suggest that the properties of radioprotection and chemoprevention exhibited by the phosphorothioate (WR-2721) and associated aminothiol (WR-1065) and disulfide (WR-33278) metabolites may be mediated via endogenous spermine-like polyamine processes. Such a mechanism would have important implications with respect to the design and development of new generation drugs for use in radioprotection and chemoprevention

[en] The contribution of G₂ cell cycle checkpoint control to ionizing radiation responses was examined in ten human tumor cell lines. Most of the delay in cell cycle progression seen in the first cell cycle following radiation exposure was due to blocks in G₂ and there were large cell line-to-cell line variations in the length of the G₂ block. Longer delays were seen in cell lines that had mutations in p53. There was a highly significant inverse correlation between the length of G₂ delay and the frequency of unrejoined chromosome breaks seen as chromosome terminal deletions in mitosis, and observation that supports the hypothesis that the signal for G₂ delay in mammalian cells is an unrejoined chromosome break. There were also an inverse correlation between the length of G₂ delay and the level of chromosome aneuploidy in each cell line, suggesting that the G₂ and mitotic spindel checkpoints may be linked to each other. Attenuation in G₂ checkpoint control was not associated with alterations in either the frequency of induced chromosome rearrangements or cell survival following radiation exposure suggesting that chromosome rearrangements, the major radiation-induced lethal lesion in tumor cells, form before cells enters G₂. Thus, agents that act solely to override G₂ arrest should produce little radiosensitization in human tumor cells

[en] Fluorescence in situ hybridization procedures were used to examine the influence of chromosome locus on the frequency and type of chromosome aberrations induced by ⁶⁰Co γ rays in the human lymphoblastoid cell line TK6. Aberrations involving the X chromosome were compared to those involving the similarly sized autosome chromosome 7. When corrected for DNA content, acentric fragments were induced with equal frequency in the X and 7 chromosomes. Dose-dependent increases in chromosomal interchanges involving chromosome 7 were noted, and the frequencies of balanced translocations and dicentrics produced were approximately equal. Chromosome interchanges involving the X chromosome were rare and showed no apparent dose dependence. Thus, while chromosomes 7 and X are equally sensitive to the induction of chromosome breaks, the X chromosome is much less likely to interact with autosomes than chromosome 7. The noninvolvement of the X chromosome in translocations with autosomes may reflect a more peripheral and separate location for the X chromosome in the mammalian nucleus. 20 refs., 2 figs., 1 tab

[en] The Chinese hamster ovary cell line CHO-T510 contains a single copy of a stably integrated retroviral vector with a selectable marker, the E. coli xanthine-guanine phosphoribosyl transferase (gpt) gene. Previous studies on the CHO-T510 line showed that, in comparison with other genetic loci, the gpt locus was hypersensitive to mutation induction by ionizing radiation. Southern blot analyses of a set of 20-26 gpt^- mutant lines, isolated as either spontaneous, gamma-induced, or alpha-radiation-induced mutants, indicated that 86-95% of these were complete vector deletions. The integrated gpt vector was localized by in situ hybridization to the q arm of chromosome 5 in close proximity to the interstitial ttelomeresequences near the pericentric region of this chromosome. One to three kilobases of sequences adjacent to the gpt integration site were clones and analyzed. Both the right and left integration sites contain sequences that hybridize to a pantelomere probe, suggesting that the vector has acquired telomeric repeats at its ends. The radio-sensitivity of the gpt locus may be due to these telomere repeats, as interstitial telomeres have been reported to be radiation-sensitive fragile sites. The gpt locus in the T510 line affords a unique resource to test this hypothesis

[en] The deuterium quadrupole coupling constant, χ_D, in the PDO₃^2- anion has been measured in solution by NMR spin-lattice (T₁) relaxation time measurements and it has been calculated via ab initio methods. The experimental value of 94.7 ± 0.5 kHz is in excellent agreement with the ab initio value of 95.0 kHz. The activation energy for the ion reorientation is 2.23 ± 0.01 kJ mol^-1

[en] Human peripheral blood T lymphocyte subpopulations were identified and isolated on the basis of their ability to bind IgG (T-G), IgM (T-M), or neither immunoglobulin class (T-null). Lymphocytes were exposed to 0, 0.5, 1.0, 2.5 or 5.0 Gy of ₆₀Co ß-rays either as a T-cell suspension or as separated T cell subsets. Survival curves, determined 5 days after irradiation, revealed that each subset has radiosensitive and radioresistant portions, and that the T-G cell is the most sensitive subset. Mitotic indices of 48-h cultures showed that the response of unirradiated T lymphocytes to PHA varied greatly among the subsets, the highest indices being obtained for the T-M and the lowest for the T-G cells. With the possible exception of the T-G cells, the subsets are realtively resistant to mitotic effects of ß-rays. T-G cells suppress the PHA-induced mitotic response of the other T lymphocyte subsets, and this suppressor effect is radiosensitive, being abolished by 1.0 Gy. It is concluded that lymphocytes exposed to >= 1 Gy of ß-rays will have very few dividing B lymphocytes or T-G cells. This together with radiation-induced loss of T-G suppressor action means that the predominant lymphocyte types in mitosis after >=1 Gy are the radioresistant T-M and T-null cells. (orig.)

No abstract available

[en] To investigate whether a delay in the rejoining of radiation-induced strand breakage can lead to sister chromatid exchange formation, Chinese hamster ovary cells were prelabeled with 5-bromodeoxyuridine and X-irradiated in the presence of 3-aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase. The resulting sister chromatid exhange frequencies were consistent with those expected if 3-aminobenzamide and X-ray treatments were independent and additive. A similar but much smaller additive effect was also observed in cells cultured in the presence of 3-aminobenzamide and X-irradiated immediately before the addition of bromodeoxyuridine to the culture medium. These findings support previous studies indicating that X rays are poor inducers of sister chromatid exhanges and suggest that the normally rapid resealing of DNA strand breaks does not account for this inefficiency

[en] The inherent radiation sensitivity of the cells within a tumor is thought to contribute to the success or failure of radiation therapy. In vitro studies have shown that differences in the radiation sensitivity of squamous cell carcinoma cell lines reflect alterations in DNA repair. These alterations result from constitutive changes in chromosome organization, not radiation-inducible processes. While inducible responses may play some role in the radiation response of tumor cells, there is no evidence for their involvement in inherent differences in tumor cell radiosensitivity or in the success or failure of radiotherapy of squamous cell carcinomas. 21 refs., 1 fig., 1 tab