Biophysik

Decay of radioactive isotopes by K-capture leads to the Auger effect and results in the loss of several orbital electrons and the emission of X-rays. Whereas radiation effects are produced from the emitted electrons, the consequences of the Auger effect are strictly localized to the site of the decaying nuclide. The paper reviews the biological consequences of the decay of125I which produces the Auger effect. Nearly all data were obtained from DNA labeled with125I-5-iodo-2′-deoxyuridine (IUdR) in bacteria and mammalian cells. Parameters of effects were cell death, DNA strand breaks, and mutation induction. In order to recognize in a cell the contribution from the Auger effect and that of absorbed radiation, experimental data are analysed in terms of the specific energy for the nuclear volume which contains the isotope. The data indicate that decay of125I is far more toxic than is expected on the basis of absorbed dose to the labeled nucleus. Moreover, it is emphasized that the toxicity of the125I decay is largely determined by events immediately localized to the site of decay. Because the consequences of the Auger effect are strictly localized to the molecular site of the decay,125I and perhaps other nuclides decaying by K-capture promise to be interesting tools in cell biology and molecular biology. First data on the Auger effect as a tool are summarized. It appears that recognizable biological damage is only observed when the Auger effect takes place in vitally important molecules, an example of which is DNA.

The Auger electron emitter 123I was examined in the form of 4-[123I]iodoantipyrine and as [123I]NaI for its effectiveness in killing cells of different sensitivity to photon irradiation. Micronucleus assays showed that 4-[123I]iodoantipyrine is 2–3 times more effective in cell inactivation than [123I]NaI. This can be attributed to the fact that antipyrine, for reason of its lipid solubility, can enter cells and can reach the nucleus, whereas [123I]NaI is excluded from the cytoplasm. In the nucleus Auger decay is conceivably located on the DNA where it may invoke high-LET irradiation damage. Irradiation damage by [123I]NaI is by long range Auger and internal conversion electrons and hence less densely ionising. Results of the present study demonstrate, however, that the enhancement of micronuclei frequency (MNF) seen with 4-[123I]iodoantipyrine as compared to [123I]NaI is similar for all cell lines and that the ratio of 4-[123I]iodoantipyrine/[123I]NaI MN response remains the same. Experiments with the free radical scavenger DMSO, indicated nearly identical dose reduction factors for both 123I carriers. These two observations strongly suggest that the cell inactivation by 4-[123I]iodoantipyrine is not by direct high-LET ionisation of DNA, but is due to an indirect effect. The indirect radiation effect of Auger decay in the nucleus could arise because 4-[123I]iodoantipyrine is not incorporated into the DNA, but is only associated with chromatin where the DNA is shielded by histones.

Experimental results obtained with the neutral sucrose gradient sedimentation techniques of analysing mammalian DNA after irradiation in vivo (Chinese hamster cells V79) are evaluated theoretically in order to verify and extend a model by Ormerod and Lehmann that describes the gradual release of free DNA from the DNA-membrane complex. The model is based on the idea of chromatin organization in the form of membrane attached superstructure units (MASSUs) defined by consecutive attachment points in intervals ofM 0 (DNA molecular weight of a MASSU). DNA sedimentation after cell lysis with sarkosyl as detergent allows good separation of the released free DNA from that remaining in the complex. The dose-dependence of both the percentage of DNA released and pertinent molecular weight parameters as measured with X-rays and derived from the model confirms it and yields the MASSU sizeM 0 = 2.4 × 109 g/mol. Furthermore, the model is evaluated with respect to high-LET radiations by a mathematical theory based strictly on microdosimetry. This approach, which could be of general interest as a contribution to theoretical microdosimetry, reduces the measurable quantities explicitly to the single event distribution of lineal energy for the gross volume,V, occupied by a MASSU in the interphase nucleus. Experimental results obtained withα-particles agree with this extended version of the model, yielding 0.2 – 0.3 µm for the diameter ofV. In summary, the following conclusions are drawn: The entire chromatin, at least the greater part of it, must be organized in regular superstructure units with no detectable variance of their lengthsM 0, which is suggested to be a general principle whose functional implications remain to be elucidated.

Es wird eine Beschreibung der normalen Reizantworten der erregbaren Membran vorgeschlagen, der die Messung der Strom-Spannungscharakteristik zugrunde liegt.

Das System Hydroxylapatitkristallite in einer geeigneten Lösung stellt in gewisser Hinsicht einin vitro-Analogon für den Knochenstoffwechsel der Erdalkalien dar. Es wird über Versuche berichtet, Unterschiede im Verhalten von Ca, Sr, Ba und Ra in synthetischem Hydroxylapatit festzustellen. Dazu wurden die Diskriminierungsfaktoren von Ca gegen Sr, Ba und Ra bei der Herstellung der Kristallite gemessen. Weiterhin wurde der Austausch der Erdalkalien zwischen vorgefertigten Kristalliten und einer geeigneten Lösung über eine Zeitdauer von 1000 h verfolgt. Die Diskriminierungsfaktoren nehmen mit zunehmender Ionengröße in der Reihenfolge Sr, Ba, Ra zu. Während Sr, Ca-Ionen auch im Inneren der Kristallite ersetzen kann, sind Ba und Ra fast ausschließlich auf die Oberfläche beschränkt. Für die Diskriminierung des Gesamtknochens muß angenommen werden, daß zusätzliche Prozesse eine Rolle spielen.