125Iodine decay in DNA: a discussion of its effectiveness for the breaking of DNA strands.

125I incorporated in DNA is known to be exceptionally toxic. Values of D0 range from about 40 to about 90 decays for survival of mammalian cells. The effectiveness of 125I in DNA with respect to the induction of breaks of the DNA strands, however, appears to be comparatively low. The numbers of strand breaks per energy deposited in subnuclear cellular structures such as DNA is smaller for a disintegration of 125I than for gamma-rays. The difference in effectiveness diminishes with increasing mass of the considered sensitive volume. The apparent inefficiency of 125I-decay may, on one hand, result from a waste of local energy deposition. On the other hand, it may be caused by a multitude of local strand breaks (clusters) induced by 125I-decay which are measured as one break only by the conventionally applied techniques of strand break measurement. The apparent inefficiency of 125I may be evidence furthermore for the importance of considering not only the DNA as the sensitive target but with equal pertinence the gross sensitive volume, i.e. the whole cell nucleus. Further, for drawing meaningful comparisons, it may be necessary to take into consideration the microdosimetric event size distributions for the critical targets.

The oxygen enhancement ratio for single- and double-strand breaks induced by tritium incorporated in DNA of cultured human T1 cells. Impact of the transmutation effect.

The effect of oxygen, expressed as the oxygen enhancement ratio (OER), on the number of single-strand breaks (SSB) and double-strand breaks (DSB) induced in DNA by the radioactive decay of tritium was measured in human T1 cells whose DNA had been labeled with tritium at carbon atom number 6 of thymidine. Decays were accumulated in vivo under aerobic conditions at 0-1 degrees C and at -196 degrees C and in a nitrogen atmosphere at 0-1 degrees C. The number of SSB and DSB produced was analyzed by sucrose gradient centrifugation. For each tritium decay there were 0.25 DSB in cells exposed to air at 0-1 degrees C and 0.07 in cells kept under nitrogen, indicating an OER of 3.6, a value expected for such low-LET radiation. However, for each tritium decay there were 1.25 SSB in cells exposed to air at 0-1 degrees C and 0.76 in cells kept under nitrogen indicating an OER of only 1.7. The corresponding values for 60Co gamma radiation, expressed as SSB per 100 eV absorbed energy, were 4.5 and 1.0, giving an OER of 4.5. The low OER value found for SSB induced by tritium decay can be explained if 31% of the total SSB produced in air result from transmutation by a mechanism which does not produce DSB and is unaffected by oxygen.

DNA strand breakage and repair in human kidney cells after exposure to incorporated iodine-125 and cobalt-60 gamma-rays.

Biological effects of 125I incorporated into DNA exceed those to be expected from the absorbed radiation dose by a factor 3--30. The reason for this discrepancy suggests special mechanisms introduced by 125I transmutation, decays by K-capture leading to the emission of an average of 6 low energy electrons including Auger electrons and to a highly positively charged daughter nuclide. The effect of 125I decay on DNA strand breakage and subsequent repair was studied. Human kidney cells T in the deep frozen state (-196 degrees C) were exposed to incorporated 125I and 60Co gamma-rays. The number of DNA single strand breaks (ssb) was determined by DNA centrifugation in alkaline sucrose gradients. DNA repair was studied by incubating the cells after thawing at 37 degrees C. For 125I decay in frozen cells which were kept with or without dimethyl-sulfoxide, 4 and 6 ssb were measured per decay. The gamma-rays produced 1ssb per 26 eV absorbed energy. Most of this damage was repaired 30 to 40 min after onset of incubation. No repair of the damage caused by 125I was observed. The high efficiency of 125I decays for the production of unreparable ssb provides evidence for the high radiotoxicity of this isotope. The observed lack of repair may in part be due to the high numbers of at least 2,000 125I decays per cell nucleus necessary for the assay system. Damage from many 125I decays may interfere with enzymatic repair processes.

The bromine enhancement ratio in mammalian cells in vitro and experimental mouse tumours.

Human kidney cells in culture and cells of mouse sarcoma-180 were allowed to incorporate bromine into their DNA. Cultured cells with and without incorporated BUdR were irradiated with electromagnetic radiations ranging in energy from 12 keV X-rays to 60Co gamma-rays to find out whether or not there exists any energy dependence of the bromine dose enhancement ratio BER. Such a dependence should show in the immediate neighbourhood of the K-absorption edge of bromine (13.5 keV). Any influence of the Auger effect triggered in bromine by external irradiation should show by a significant increase of the BER for energies rising from slightly below to slightly above the bromine K-edge. Values of D37, D0 and the extrapolation numbers of the cell survival curves served as biological endpoints. Measured values of BER ranged from 1.12-2.00 without any significant dependence energy. A weakly pronounced peak was found for 50 kV X-rays of 26 keV mean energy. Sarcoma-180 were irradiated with 14 kEV X-rays and 60C gamma-rays. BUdR was administered i.v., i.p. and directly into the tumours in quantities of up to 1 ml of a 10(-3) M solution. Tumour regression caused by the irradiations served as a measure of the radiation effects with and without incorporated BUdR. No significant dose enhancement effect of bromine was observed in this case. Within error limits, the combination of BUdR with 14 keV X-rays proved more effective than BUdR combined with 60Co gamma-rays.

Calculation of specific energies of incorporated 239Pu and 131I in accordance with the concept of the critical cell.

A better understanding of the effects of energy deposited in cells by incorporated isotopes can be expected from an analysis of differential cell doses. With this thought in mind, the distributions of specific energies in tissue were calculated for 239Pu and 131I. A program written in Fortran IV makes use of a matrix of spherical cells and cell nuclei of 10 and 8 mum diameter, respectively. The cells are arranged in close-packed structure. The radioactivity is considered as being compiled to point sources of 1 dps activity. The sources are located in the common centers of cells and nuclei. The calculations yield discrete values of specific energy using the mass of the nuclei for mass of reference. The numbers of cell nuclei receiving given amounts of specific energy are functions of the specific activity of the isotopes in the tissue. The specific activity is varied by changing the number of sources per g of tissue. The program also allows to calculate the numbers of cell nuclei with zero energy deposition. From the 1 dps point sources an average specific energy of 831 rads/h results for plutonium for cell nuclei within the range of the 5.14 MeV alpha-particles. For iodine, the value is 35 mrads/h within the range of the beta-particles of 188 KeV mean energy. If the volumes irradiated by the sources begin to overlap these values begin to increase accordingly.

The RBE of 2.2-BeV protons for 30-day lethality in mice.

BNL Swiss Albino mice were exposed (five in tandem) in a 2.5-cm I.D. Lucite tube to a parallel beam of 2.2-BeV protons. The LD5o was 1.81+/-0.03 X 10(10) p/cm(2), or 641 rads. The corresponding LD50 for 250-kVp x-rays was 557 rads, yielding an RBE of 0.87. No difference in time pattern of death was observed between the x-irradiated and proton-irradiated animals. It is concluded that, with the exposure geometry used in these experiments, ionization by primary and high-energy secondary protons was the major dose constituent. A comparison is made with other experiments on the lethal effects of protons in which different geometries were employed. There is evidence that, with exposure in material of larger diameter in which there is a larger contribution to dose from lateral scatter, high-LET components of the beam may play a more dominant role. It was also observed in these experiments that the presence of Pseudomonas aeruginosa may result in a lower LD50 and "early death," following either x-irradiation or proton radiation. This may have accounted for some of the "early deaths" following proton irradiation reported earlier.