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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

Proton magnetic resonance studies of 5,6-saturated thymidine derivatives produced by ionizing radiation. Conformational analysis of 6-hydroxylated diastereoisomers.

The conformational properties of ten 6-hydroxylated dihydrothymidine derivatives including the various diastereoisomers of 5,6-dihydroxy-5,6-dihydrothymidine, 6-hydroxy-5,6-dihydrothymidine and 5-bromo-6-hydroxy-5,6-dihydrothymidine have been studied by 250 MHz proton magnetic resonance in aqueous solutions. A close correlation has been established between the carbon-6 configuration and the osidic conformation. The increase in the amplitude of the puckering within the furanose ring compared to that of thymidine or 2'-deoxyuridine is more pronounced for the levorotatory (6S) nucleosides than for the dextrorotatory (6R) diastereoisomers. The importance of the 2' endo conformer population decreases in the following order: (-) greater than (+) greater than thymidine. The absence of destabilizing effects on the g+ rotameric population about the C(4')-C(5') bond denotes the lack of any interaction between the exocyclic hydroxymethyl group and the 6-hydroxyl function or the 2-keto group. The 5,6-saturated nucleosides adopt a preferential anti conformation. The comparison has been extended to syn nucleosides which show opposite trends in the sugar conformation and g+ distribution.

Magnetic Resonance Spectroscopy

[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