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Studies on the sterilization of pharmaceutical base materials with ionizing radiation and ethylene oxide.

The use of ionizing radiation and ethylene oxide for the sterilization of pharmaceutical base materials of animal origin, used to produce organopreparations, was studied. The materials included liver extract, pancreas extract, dried thyroid and intrinsic factor. The effective sterilizing doses for the examined materials and dependence between effective ionizing radiation dose and primary contamination were determined.

Animals

Ionizing radiation perturbs the switch-on of transcriptase in a model transcription complex in vitro.

Ionizing radiation markedly alters the response of the reovirus transcriptase unblocking mechanism to stimulation by K+ ions, which normally trigger the switch-on of transcription in this system. In irradiated subviral particles the concentration of K+ ions needed to trigger switch-on is reduced in a dose-dependent way. The observed alteration of switch-on characteristics appears to correlate with alteration of the electrophoretic behaviour of a single major polypeptide species. These observations have important implications for understanding some of the effects of ionizing radiation on cells, most notably the induction of both latent virus and cell differentiation.

DNA-Directed RNA Polymerases

[The problems raised by the irradiation of pregnant women. Effects of ionizing radiations on the embryon and foetus (author's transl)].

In man, the period of maximum risk for the embryo and foetus is between the second and tenth week after conception. The most frequent and most severe malformation is microcephaly which in extreme cases is accompanied by mental retardation. The results of studies in experimental animals and man agree that it is impossible to demonstrate any increased risk of malformation with doses below 15 rads, and that the increase over the spontaneous incidence of malformation is slight at doses below 25 rads. A very small increase in the frequency of leukaemias and cancers has been observed after irradiation in utero for pelvimetry, which delivers a few rads; it can be estimated from these data that a dose of 2 rads induces at the most the risk of one case of cancer in 2,000 children. In practice, it is only exceptionally that an abortion is advised after a diagnostic radiological examination, since the doses in these circumstances are relatively low. A therapeutic termination of pregnancy should be advised when the dose is greater than 20 rads, but it is necessary to take into account other medico-social factors. Conversely, it is important to avoid any irradiation in women who could be pregnant and in particular avoid any irradiation of the true pelvis during the 10 days prior to menses and especially if there has been a delay in the start of menstruation. In pregnant women radiological examinations should only be made if they are of paramount importance for the mother, and all precautions taken to reduce the dose to the uterus in the absolute minimum.

Abnormalities, Radiation-Induced

Quantitative relationships of the harmful effect of ionizing radiation on natural resistance of the organism to various infectious agents. Review of literature.

On the basis of an analysis of data from the literature and our own experimental results, the conclusion can be drawn that there is inverse linear dependence between the dose of irradiation and natural resistance of the organism to infection with various infectious agents. With increasing doses of irradiation, the irradiated organism is exposed to greatest risk from the part of the agents of intestinal infections and representatives of normal microflora. These are followed by agents of various diseases of microbial nature. The least decrease can be observed in resistance to viruses.

Animals

Epigenetic alterations induced by ionizing radiation: pathways to cancer and prognostic strategies.

PURPOSE: Ionizing radiation (IR) is widely used not only in cancer diagnosis and therapy, but its biological effects also extend beyond radiation-induced lethal lesions, e.g., specifically DNA double-strand breaks (DNA-DSBs). This review aims to summarize current evidence on IR-induced epigenetic alterations and to integrate mechanistic insights from radiation chemistry and radiation biology that link DNA damage to long-term epigenetic dysregulation. RESULTS: Experimental and clinical studies collectively show that IR induces persistent epigenetic reprogramming, including global and gene-specific DNA methylation changes, radiation-responsive histone modifications, chromatin remodeling, and dysregulation of non-coding RNAs. Aberrant RNA methylation, including modifications like N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanine (m7G), and N3-methylcytosine (m3C), is closely linked to tumorigenesis and progression. Due to its tumor-specific properties, RNA methylation markers, specifically m6A, m5C, m1A, m7G, and m3C, emerge as valuable markers in liquid biopsy. Radiation chemistry studies indicate that epigenetically modified bases, for example, m5C, are preferential targets of radiation-induced oxidative damage, thereby promoting mutational hotspots and genomic instability. By altering DNA repair, apoptosis, immune responses, and cellular differentiation, these epigenetic changes promote carcinogenesis, radioresistance, and tissue toxicity. CONCLUSION: IR-induced epigenetic alterations represent a critical interface between initial DNA damage and long-term biological outcomes. Improved understanding of radiation-associated epigenetic signatures may enhance risk assessment, inform prognostic stratification, and support the development of epigenetic-targeted strategies to optimize radiotherapy and reduce adverse effects.

Ionizing radiation

Ionizing radiation damage to the folded chromosome of Escherichia coli K-12: repair of double-strand breaks in deoxyribonucleic acid.

The extremely gentle lysis and unfolding procedures that have been developed for the isolation of nucleoid deoxyribonucleic acid (DNA; K. M. Ulmer et al., J. Bacteriol. 138:475-485, 1979) yield undamaged, replicating genomes, thus permitting direct measurement of the formation and repair of DNA double-strand breaks at biologically significant doses of ionizing radiation. Repair of ionizing radiation damage to folded chromosomes of Escherichia coli K-12 strain AB2497 was observed within 2 to 3 h of post-irradiation incubation in growth medium. Such behavior was not observed after post-irradiation incubation in growth medium of a recA13 strain (strain AB2487). A model based on recombinational repair is proposed to explain the formation of 2,200 to 2,300S material during early stages of incubation and to explain subsequent changes in the gradient profiles. Association of unrepaired DNA with the plasma membrane is proposed to explain the formation of a peak of rapidly sedimenting material (greater than 3,100S) during the later stages of repair. Direct evidence of repair of double-strand breaks during post-irradiation incubation in growth medium was obtained from gradient profiles of DNA from ribonuclease-digested chromosomes. The sedimentation coefficient of broken molecules was restored to the value of unirradiated DNA after 2 to 3 h of incubation, and the fraction of the DNA repaired in this fashion was equal to the fraction of cells that survived at the same dose. An average of 2.7 double-strand breaks per genome per lethal event was observed, suggesting that one to two double-strand breaks per genome are repairable in E. coli K-12 strain AB2497.

Cell Nucleus