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 Table of Contents  
Year : 2016  |  Volume : 7  |  Issue : 2  |  Page : 60-61

Synergistic interaction and cell responses to environmental factors

From the Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Radiation Signalling and Cancer Biology Section, Mumbai, Maharashtra, India

Date of Web Publication7-Oct-2016

Correspondence Address:
Amit Kumar
From the Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Radiation Signalling and Cancer Biology Section, Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-0168.191705

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How to cite this article:
Kumar A. Synergistic interaction and cell responses to environmental factors. J Radiat Cancer Res 2016;7:60-1

How to cite this URL:
Kumar A. Synergistic interaction and cell responses to environmental factors. J Radiat Cancer Res [serial online] 2016 [cited 2023 Feb 5];7:60-1. Available from:

Authors: Vladislav G. Petin and Jin Kyu Kim

Published: Nova Science Publishers, Inc. NY

Pages: 331

Year: 2016

ISBN: 978-1-63483-499-5

Safety standard for the risk assessment of human health is largely based on the assumption that the agents under consideration act independently from each other. However, in practical scenarios, multiple agents exert their effects on model organism, and synergistic or antagonistic interaction may occur, which has not been given due importance in literature. The book authored by Petin and Kim fulfills this gap and identifies the significance of such synergistic interaction and developed mathematical models to investigate the mechanism of such interaction. To quantitatively describe synergistic interaction, the book used data from several studies performed in microorganism, unicellular eukaryotes, yeast cells, mammalian cells, and human.

The book developed a mathematical model for quantitative description of cell's responses to ionizing radiation. The model combines the fundamental hit-and-target principles and biological stochastic. The attractiveness of this developed "probability model" is that it can be utilized to predict diverse radio responses of eukaryotic cells. In addition, this chapter estimates the relative biological effectiveness (RBE) of densely ionizing radiation for both wild type and radiosensitive mutant of yeast cells, which depends on physical characteristics of radiation and cell's recovery ability (determined by recombination repair mechanisms). RBE for cells in different phases of growth (e.g., stationary or exponential) has also been estimated. A mathematical approach has been suggested to explain various shapes of the dose-effect curve for eukaryotic cells.

In Chapter 2, the book illustrates the association between radioprotective action of thiol compounds (e.g., cysteine, cystamine, and cysteamine) and cell repair capacity for wild-type and radiosensitive diploid yeast cells. Herein, the effect of compounds was found more prominent for diploid and wild-type yeast cells than the haploid and mutant cells. Such association was not observed for haploid yeast cells. Radiosensitization of hypoxic yeast cells by oxygen and electron-affinic compounds (metronidazole and misonidazole) was compared for wild-type and various radiosensitive yeast mutants. Radiobiological parameters for yeast cells and oxygen enhancement ratio and enhancement ratio were determined for these compounds under oxic and hypoxic conditions. These parameters suggest a rational need for more effective hypoxic radiosensitizers for the improvement of cancer radiotherapy in clinic. Importantly, a novel effort was also made to analyze the contribution of cell repair mechanism (recovery system) in the modification of cellular radiosensitivity.

Chapter 3 demonstrates interesting observations about the antagonistic interaction between densely ionizing radiation (alpha particle) and ultraviolet (UV)/visible light. It was analyzed that UV light exposure mitigates the lethal effect of ionizing radiation in yeast cells, which is independent of the sequence of these applied radiations and yeast's ploidy level. These observations were explained by previously recognized mechanism of "photoreactivation" which induces by Ĉerenkov radiation component during traversal of charged particle in the medium. The role of such Ĉerenkov radiation-induced damage/events (UV-like damage) was also discussed in the manifestation of mechanism of low-dose radiation responses such as adaptive reaction, bystander effect, and radiation hormesis. This discussion would lead to the discovery of new mechanisms activated by such events, which seem to be relevant to radiation risk assessment and in understanding the role of radiation hormesis in the people of high background radiation areas.

The book analyzed the mechanism of synergistic interaction between ionizing radiation/UV light and heat (hyperthermic stress) in yeast cells. Data analysis elucidated the role of enhanced yield of irreversible damage by hyperthermic treatment rather than the impairment of recovery (repair) process itself in the enhancement of cytotoxicity by combined action of radiation and heat. The book also concluded that synergistic effect of combined action of chemical and ionizing radiation in mammalian cells is also attributable to the increased yield of irreversible damage. It has been discussed that cellular thermotolerance is not always associated with the level of heal shock proteins, and other mechanism/factors need to be considered for thermosensitivity of cells. Despite the importance of synergistic interaction, a set of general rules was missing in literature regarding the response of various unicellular organisms/mammalian cells to combined action of hyperthermia and physical factors (e.g., ionizing radiation, UV light, or ultrasound). The book fulfills this gap of knowledge and devises several universal rules of synergism, for example, synergistic interaction occurs within a certain temperature range, which becomes maximum at a specific temperature. The book proposed a conceptual idea and mathematical model based on experimental data to explain the general principles of synergistic interaction. This theoretical conception suggested the mechanism of synergistic interaction, which states that the synergy is conditioned by the additional effective damage arising from the interaction of sublesions induced by both agents. These sublesions are considered as noneffective when each agent applied individually. This concept would help in the assessment of harmful effects arising from combined action of factors (e.g., ionizing radiation/UV exposure and heat). In addition, a semi-empirical mathematical model was applied to describe, predict, and optimize the synergistic interaction of simultaneous action of ionizing radiation and heat to the simple microorganisms.

Finally, the book presents a good review of synergistic interaction in human. Several studies have been analyzed, for example, interaction between ionizing radiation and UV exposure for skin carcinogenesis, interaction between radiation exposure and industrial dust/fibers for lung cancer, interaction between epidemiologically proven metal carcinogen (arsenic, nickel, antimony, etc.) and high LET radon exposure for lung cancer in miners, and interaction between radon exposure and smoking for lung cancer. The later was found to be synergistic (greater than additive) for the risk of lung cancer. In view of these observations, the book highlights the importance of recommendations to resettle the people in the United States from the areas where the radon concentration exceeds 148 Bq/m 3 . The book used the data of Swedish Cancer Registry to calculate the synergistic enhancement ratio for interaction between radon exposure and smoking for the risk of lung cancer. Similarly, parameters of synergistic interaction were elucidated using data available from other human studies, for example, risk of laryngeal/oral cancer due to combined effect of smoking and alcohol and risk of lung cancer in uranium miners with tobacco smoke inhalation. Thus, in summary, the book presents mathematical model/approach of synergy to explain the unusual situation in radiobiology when low-dose radiation exposure in combination with small internal contamination could be worse than that obtained at high radiation doses. This monograph would be useful for researchers in the field of radiobiology, medical physics, medicine, toxicology, radiation protection, and ecology.


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