Biomedical subjects
Publications and source records attributed to H Dertinger.
The therapeutic value of pion irradiation was critically challenged by examining, in a cell culture system, various parameters of biological significance such as relative biological efficiency (RBE), oxygen enhancement ratio (OER), DNA-break formation, changes in cell cycle kinetics and regrowth. In all parameters, pions were superior to conventional low-LET radiation.
Spheroids of V79 cells were irradiated with 180 MeV/c pi--mesons in the peak region and with gamma-rays. Doses of 900 and 1500 rad were applied, respectively, yielding 14% surviving cells. Regrowth of the spheroids was followed by measuring volume changes, cell multiplication as well as viability and proliferation of cycling and resting spheroid cells. While volume growth after irradiation was equal for both radiations, the time profiles of cell density, viability and mean DNA content per cell were found to be different. Consistently, a more prompt and pronounced response to pion irradiation could be inferred and was discussed in terms of LET dependent proliferation and elimination of inactivated cells and their subsequent substitution by viable progeny cells. Recruitment of resting cells was observed with both radiations.
Spheroids of V79 cells were subjected to fractionated irradiation with two doses of gamma-radiation. In addition, a two hours hyperthermic treatment at 42 degrees C immediately following the first dose was applied. Cycling and resting cells of this in-vitro tumour model were then assayed for survival as function of the fractionation interval. In parallel, changes in cycle progression between the doses were measured by means of cytofluorometry. As main proliferative effects induced by this combined radiation and heat treatment transient S-phase blocking of cycling and recruitment of resting cells were observed. The split-dose survival curve displayed considerable synergistic action of heat and radiation and a six hours delay of Elkind-recovery in both cycling and resting cells.
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Monolayers and spheroids of Chinese hamster cells (V79) were subjected to negative pion irradiation under aerobic conditions. R.b.e. values in the pion peak of 1-8 and 1-5 were obtained for monolayers and spheroids, respectively, whereas the r.b.e. for the plateau was found to be slightly higher than 1. In addition, it was observed that the higher resistance of the V79 spheroid cells than the monolayers to gamma-irradiation is not diminished in the pion peak, suggesting that the underlying phenomenon of intercellular communication influences cell survival even after high-LET irradiation.
It is shown by UV absorption and absolute fluorescence spectroscopy of solutions containing both DNA and quinacrine that the components experience mutual radio-protection due to scavenging of water radicals. From measurements at different ionic strengths it is inferred that quinacrine bound to DNA is more efficiently protected than the free compound. Furthermore, release of bound quinacrine from DNA is observed at higher doses.
Strand breakage of DNA irradiated in solution and in the dry state in the presence of quinacrine was investigated by sedimentation analysis. Determination of single strand breaks in solution combined with binding studies permits to conclude that bound quinacrine protects DNA more effectively than the free compound. In the dry state quinacrine is without detectable effect on both single and double strand break formation, neither under aerobic nor anaerobic conditions.
Strand break formation and biological inactivation of infectious DNA of bacteriophage phi chi 174 exposed to vacuum-ultra-violet radiation of 4-9 to 21-2 eV quantum energy is investigated. At 21-2 eV as many as 84 per cent of the DNA molecules are inactivated by breaks whereas breaks do not contribute to inactivation at 4-9 eV. The quantum yield of break formation increases from 1-7 X 10(-5) (4-9 EV) to 0-55 (21-2 eV) and shows a dependence on energy similar to that of electron emission (due to ionization) above 8 eV. The mechanisms leading to break formation and inactivation are discussed taking the absorption spectrum of DNA in the vacuum-ultra-violet region into consideration.
Post-irradiation growth kinetics of gamma-irradiated spheroid and monolayer cells in exponential growth phase was investigated by means of dose-response curves based on cell counts after specified time intervals following irradiation. A mathematical model of cell-growth after irradiation was fitted to these curves. The model parameters (related to division delay and growth of non-surviving cellsy obtained from this analysis consistently indicate increasing resistance to sub-lethal damage of cells cultured as multicellular spheroids under conditions of increasing three-dimensional contact. In contrast, no indication of an increased radiation-resistance was found with cells cultured on a substratum under a variety of conditions.
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