Comparison of the Combined Effects of Hyperthermia with Ionizing Radiation or Cisplatin on Yeast and Mammalian Cells

Author(s):  
М. Пронкевич ◽  
M. Pronkevich ◽  
Е. Евстратова ◽  
E. Evstratova ◽  
С. Белкина ◽  
...  

Purpose: To compare radiation responses of yeast and mammalian cells to combined actions of various agents and on this basis to draw a conclusion about the possibility of synergy ideas application in medical radiology. Material and methods: The yeast cells of Saccharomyces cerevisiae were exposed to the combined action of hyperthermia (22–58 °C, exposure time 0–9 hrs) with ionizing radiation (25 MeV bremsstrahlung 5 and 25 Gy/min or γ-rays 60Co, 2, 10, and 80 Gy/min, acute irradiation) or anti-tumor drug cisplatin (0,05 or 0,25 mg/ml, exposure time 0–3 hrs). The result of synergistic interaction for yeast cells was assessed by the survival curves obtained by the authors after separate exposure to hyperthermia, ionizing radiation, cisplatin and after combined action of hyperthermia with ionizing radiation or cisplatin. To quantify the synergistic interaction of similar combined actions on mammalian cells, the data published by other authors have been used who did not evaluate the synergistic effect themselves. Results: The synergistic interaction of hyperthermia with ionizing radiation or cisplatin was established for yeast and mammalian cells. It is shown that the synergistic effect of the simultaneous action of these agents is observed only within a certain temperature range, within which there is an optimal temperature at which the greatest synergism occurs. This optimal temperature is shifted to lower values with a decrease in the dose rate of ionizing radiation or concentration of cisplatin. For sequential application of hyperthermia and ionizing radiation the effect of combined action increases with an increase in acting temperature up to a certain limit, after which it remains constant. These results are interpreted using the mathematical models previously proposed, in accordance with which the synergism is determined by the formation of additional damage due to the interaction of sub-damage that are not effective after separate application of agents. Despite the fact that all of the data presented were obtained at temperatures far beyond the ambient temperature, it is not excluded that there could be optimal intensities of harmful agents existing in the biosphere and capable of interacting with physiological heat of animals and man in a synergistic manner. Hence, the assessment of health or environmental risks from numerous natural and man-made agents at the level of intensities found in environmental and occupational settings should take into account synergistic interaction between harmful agents. Conclusion: The general regularities of synergistic effects of combined action of hyperthermia with ionizing radiation or with cisplatin for yeast and mammalian cells have been established – the existence of optimal parameters for acting agents providing the highest synergy and its dependence on the intensity of agents applied.

2020 ◽  
Vol 7 (2) ◽  
pp. 82-91
Author(s):  
E. S. Evstratova ◽  
V. G. Petin

The review is devoted to the analysis of the problem of synergistic ideas application in oncology after simultaneous combined application of agents. An example of the determination and quantification of the synergistic enhancement ratio is presented. It is emphasized that independent addition is determined by product of probabilities of the effects induced by each agent applied separately. Elevated temperatures synergistically enhance the lethal effect of ionizing radiation and chemical compounds used in the treatment of cancer. Analyzing the dependence of the synergistic effect on the acting temperature after its simultaneous application with ionizing radiation or cisplatin, the existence of an optimal temperature ensuring the greatest synergistic interaction was shown for cultured mammalian and yeast cells. The universal regularities of the manifestation of synergism, independent on the agents, biological objects and tests used, are noted. The greatest synergy is observed with the simultaneous application of agents. The synergism recorded as a result of the combined effects of two factors is observed only with a certain ratio of the effects induced by each agent. Synergism depends on the intensity of the factors used — the current temperature, the dose rate of ionizing radiation or the concentration of chemical agents. These universal patterns have been demonstrated for proand eukaryotic cells, including oncological origin. The existence of universal patterns of synergism indicates the need to develop a new paradigm and theoretical model of synergism, which should take into account the identified patterns. An original biophysical concept of synergistic interaction is proposed. Concrete results are presented that demonstrate the possible ways of using the ideas of synergism in oncology by achieving the greatest synergistic enhancement ratio for the combined effects of various physical and chemical agents. It is concluded that the knowledge and the application of the ideas and general patterns of synergy described in this paper can be useful for specialists using the simultaneous action of various agents to optimize combined treatment methods in modern oncology.


2021 ◽  
Vol 7 (4) ◽  
pp. 285-290
Author(s):  
Lyudmila N. Komarova ◽  
Anzhelika A. Melnikova ◽  
Denis A. Baldov

Proton and carbon beam therapy is currently recognized as the most effective and highly accurate form of radiation therapy for deeply located tumors, including radioresistant ones. This is due to the fact that they have all the advantages of spatial dose distribution and, at the same time, are densely ionizing radiations capable of effectively affecting hypoxic, slow-growing tumors and other neoplasms that are insensitive to traditional types of radiation. It is well known that one of the main methods for treating neoplasms is chemotherapy. The predominant mechanism of action of anti-tumor drugs is the induction of DNA damage with the subsequent impossibility of repair. In our study, we used an anti-tumor antibiotic of the anthracycline series, doxorubicin. The assessment of the potential significance of the synergistic interaction of ionizing radiation with chemical preparations in medical radiology remains an urgent and unresolved problem. It is possible to achieve the maximum effect of the combined action of two agents when they act simultaneously. The phenomenon of synergy can be used to optimize the combined use of radiation and chemotherapy in clinical practice. In this regard, it seems relevant to conduct a study for HeLa cancer cells exposed to ionizing radiation, an antitumor drug, as well as their combination. In the course of the study, results were obtained on the manifestation of the synergistic nature of the agents used, which is of great practical and theoretical importance for understanding the mechanism of the combined effect of ionizing radiation and the chemotherapy drug (doxorubicin). The obtained data can be helpful in optimizing the combined effects in order to achieve maximum synergistic interaction.


1980 ◽  
Vol 18 (1) ◽  
pp. 45-55 ◽  
Author(s):  
V. G. Petin ◽  
V. P. Komarov ◽  
V. G. Skvortzov

2021 ◽  
Vol 15 (4) ◽  
pp. 575-582
Author(s):  
Iryna Koval ◽  

The paper considers water purification processes from Bacillus bacteria type under the conditions of gases bubbling only (argon, helium, oxygen, and carbon dioxide), cavitation and combined action of gas and cavitation. The synergistic effect was found under conditions of simultaneous action of gas and cavitation (kd(gas/US ) >kd(gas) + kd(US) almost double) and it was shown that kd(gas/US) >kd(gas) by almost an order of magnitude. Relative series of effective destruction of microbial cells was established: Ar/US > О2/US >Не/US > СО2/US. Destruction degree of the cells reaches 70 %at the short-term Ar/US exposure (~8 min), which is 7 times more active than cavitation action and 13.5 times more than bubbling of Aralone.


1995 ◽  
Vol 31 (5-6) ◽  
pp. 119-122 ◽  
Author(s):  
J. M. Cassells ◽  
M. T. Yahya ◽  
C. P. Gerba ◽  
J. B. Rose

Electrolytically generated copper and silver ions (400:40 and 800:80 μg/l) were evaluated, separately and combined with 1.0 mg/l free chlorine, for their efficacy in reducing the viable numbers of Naegleria fowleri amoebas in water (pH 7.3 and 23-25°C). Inactivation rates (k = log10 reduction/min) and T99 values (exposure time required to achieve a 99% or a 2 log10 reduction) of the disinfectants were determined. Copper and silver alone, at ratio of 400:40 to 800:80 μg/l caused no significant inactivation of N. fowleri even after 72 hours of exposure (k = 0.00017 and 0.00013, respectively). Addition of 1.0 mg/l free chlorine to water which contained 400:40 or 800:80 μg/l copper and silver resulted in enhanced inactivation rates (k = 0.458 and 0.515, respectively) compared to either chlorine alone (k = 0.33) or the metals alone. Water containing 800:80 μg/l copper and silver with 1.0 mg/l chlorine showed a T99 value of 3.9 minutes, while chlorine alone showed a T99 of 6.1 minutes. Enhanced inactivation of N. fowleri by a combined system of free chlorine and copper and silver may be attributed to the different mechanism that each disinfectant utilizes in inactivating the amoebas, and may suggest a synergistic effect.


1995 ◽  
Vol 108 (3) ◽  
pp. 927-934 ◽  
Author(s):  
M. Starborg ◽  
E. Brundell ◽  
K. Gell ◽  
C. Larsson ◽  
I. White ◽  
...  

We have analyzed the expression of the murine P1 gene, the mammalian homologue of the yeast MCM3 protein, during the mitotic cell cycle. The MCM3 protein has previously been shown to be of importance for initiation of DNA replication in Saccharomyces cerevisiae. We found that the murine P1 protein was present in the nuclei of mammalian cells throughout interphase of the cell cycle. This is in contrast to the MCM3 protein, which is located in the nuclei of yeast cells only between the M and the S phase of the cell cycle. Detailed analysis of the intranuclear localization of the P1 protein during the cell cycle revealed that it accumulates transiently in the heterochromatic regions towards the end of G1. The accumulation of the P1 protein in the heterochromatic regions prior to activation of DNA replication suggests that the mammalian P1 protein is also of importance for initiation of DNA replication. The MCM2-3.5 proteins have been suggested to represent yeast equivalents of a hypothetical replication licensing factor initially described in Xenopus. Our data support this model and indicate that the murine P1 protein could function as replication licensing factor. The chromosomal localization of the P1 gene was determined by fluorescence in situ hybridization to region 6p12 in human metaphase chromosomes.


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