Radiation effects induced by low doses in complex tissue and their relation to cellular adaptive responses

Feinendegen, L. E.; Bond, V.P.; Sondhaus, C. A.; Muehlensiepen, H.

doi:10.1016/s0027-5107(96)00121-2

Cited by 44 publications

(29 citation statements)

References 19 publications

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“…Exposure to low levels of IR is evidenced to generate beneficial effects for mammalian cells with respect to the maintenance of genomic integrity and the ability to repair damaged DNA [4,5]. Although the IR doses applied vary on a large scale, a similar radioadaptive resistance is significantly induced in many other species, including Escherichia coli, protozoa, algae, *Corresponding author.…”

Section: Does Ionizing Radiation (Ir) Induce Radioadaptive Resistance?mentioning

confidence: 99%

“…Such prosurvival molecular networks, especially induced in the tumor under clinical fractional irradiation, have not yet been fully elucidated. New therapeutic means including manipulating the radioadaptive response require further knowledge of the consequences of the activation of such prosurvival pathways.Exposure to low levels of IR is evidenced to generate beneficial effects for mammalian cells with respect to the maintenance of genomic integrity and the ability to repair damaged DNA [4,5]. Although the IR doses applied vary on a large scale, a similar radioadaptive resistance is significantly induced in many other species, including Escherichia coli, protozoa, algae, *Corresponding author.…”

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confidence: 99%

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NF-κB-mediated adaptive resistance to ionizing radiation

Ahmed

2008

Free Radical Biology and Medicine

198

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Ionizing radiation (IR) began to be a powerful medical modality soon after Wilhelm Röntgen's discovery of X-rays in 1895. Today, more than 50% of cancer patients receive radiotherapy at some time during the course of their disease. Recent technical developments have significantly increased the precision of dose delivery to the target tumor, making radiotherapy more efficient in cancer treatment. However, tumor cells have been shown to acquire a radioresistance that has been linked to increased recurrence and failure in many patients. The exact mechanisms by which tumor cells develop an adaptive resistance to therapeutic fractional irradiation are unknown, although low-dose IR has been well defined for radioadaptive protection of normal cells. This review will address the radioadaptive response, emphasizing recent studies of molecular-level reactions. A prosurvival signaling network initiated by the transcription factor NF-κB, DNA-damage sensor ATM, oncoprotein HER-2, cell cyclin elements (cyclin B1), and mitochondrial functions in radioadaptive resistance is discussed. Further elucidation of the key elements in this prosurvival network may generate novel targets for resensitizing the radioresistant tumor cells. KeywordsIonizing radiation; NF-κB; Signal transduction; Adaptive radiation resistance; Free radicals Does ionizing radiation (IR) induce radioadaptive resistance?Acquired tumor radioresistance can be induced during radiotherapy due to tumor repopulation [1]. Although tumor radioresistance stands as an fundamental barrier limiting the effectiveness of radiation therapy, the exact molecular mechanisms underlying the radioadaptive response are largely unknown. The term radioadaptive response was originally described as a reduced cell sensitivity to a higher challenging dose when a smaller inducing radiation dose had been applied earlier [2]. Olivieri et al. [3] first described an adaptive response of human lymphocytes to ionizing radiation. Since then a substantial number of reports make a strong case for the existence of cellular radioprotective mechanisms that can be activated in response to a small dose of ionizing radiation. It is assumed that a specific prosurvival signaling network is induced in irradiated mammalian cells. Such prosurvival molecular networks, especially induced in the tumor under clinical fractional irradiation, have not yet been fully elucidated. New therapeutic means including manipulating the radioadaptive response require further knowledge of the consequences of the activation of such prosurvival pathways.Exposure to low levels of IR is evidenced to generate beneficial effects for mammalian cells with respect to the maintenance of genomic integrity and the ability to repair damaged DNA [4,5]. Although the IR doses applied vary on a large scale, a similar radioadaptive resistance is significantly induced in many other species, including Escherichia coli, protozoa, algae, *Corresponding author. Fax: +1 765 496 1377. E-mail address: jjli@purdue.edu (J.J. Li). . In addition, h...

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Section: Does Ionizing Radiation (Ir) Induce Radioadaptive Resistance?mentioning

confidence: 99%

mentioning

confidence: 99%

NF-κB-mediated adaptive resistance to ionizing radiation

Ahmed

2008

Free Radical Biology and Medicine

198

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“…This overlap of damages has led to a controversy with respect to determining radiation risk. Proponents of a ''threshold effect'' claim that because endogenous oxidative damages are effectively repaired and adaptive responses have been demonstrated for certain radiation endpoints, then a threshold must exist for the carcinogenic and lethal consequences of ionizing radiation (5,6). This issue is an important one because much of the projected radiation exposures associated with human activity over the next hundred years will come from low doses associated with medical tests, waste cleanup, and materials associated with nuclear weapons and nuclear power.…”

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confidence: 99%

Abortive base-excision repair of radiation-induced clustered DNA lesions in Escherichia coli

Blaisdell

Wallace

2001

Proc. Natl. Acad. Sci. U.S.A.

204

112

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It has been postulated that ionizing radiation produces a unique form of cellular DNA damage called ''clustered damages'' or ''multiply damaged sites''. Here, we show that clustered DNA damages are indeed formed in Escherichia coli by ionizing radiation and are converted to lethal double-strand breaks during attempted baseexcision repair. In wild-type cells possessing the oxidative DNA glycosylases that cleave DNA at repairable single damages, doublestrand breaks are formed at radiation-induced clusters during postirradiation incubation and also in a dose-dependent fashion. E. coli mutants lacking these enzymes do not form double-strand breaks postirradiation and are substantially more radioresistant than wild-type cells. Furthermore, overproduction of one of the oxidative DNA glycosylases in mutant cells confers a radiosensitive phenotype and an increase in the number of double-strand breaks. Thus, the effect of the oxidative DNA glycosylases in potentiating DNA damage must be considered when estimating radiation risk.A pproximately 70% of radiation-induced DNA damages are formed by reactive-free radicals produced by the radiolysis of water in the vicinity of DNA (1). These radiation-induced DNA damages are repaired by base-excision repair (2) and overlap substantially with those formed during normal oxidative metabolism (3), which are produced at significant rates in unirradiated cells (4). This overlap of damages has led to a controversy with respect to determining radiation risk. Proponents of a ''threshold effect'' claim that because endogenous oxidative damages are effectively repaired and adaptive responses have been demonstrated for certain radiation endpoints, then a threshold must exist for the carcinogenic and lethal consequences of ionizing radiation (5, 6). This issue is an important one because much of the projected radiation exposures associated with human activity over the next hundred years will come from low doses associated with medical tests, waste cleanup, and materials associated with nuclear weapons and nuclear power. Whether a threshold exists for the consequences of radiation damage will significantly influence risk estimates for low-dose exposures. Currently, risk estimates for individuals or groups exposed to low radiation doses are determined from epidemiological data obtained from populations exposed to high doses, and a ''linear-no-threshold'' estimation is used for assessment. Proponents of the linear-no-threshold model hold that the biologically important radiation damages in DNA, such as double-strand breaks, are substantially different from single, repairable oxidative lesions. It also has been predicted that ionizing radiation produces a unique form of DNA damage called ''clustered damages '' (1, 7, 8). If, indeed, clustered damages can be demonstrated in living cells and if, unlike the single lesions from which they are formed, they are poorly repaired, these facts would provide additional support for the linear-nothreshold model.Modeling of radiation track structures (9, 10) ...

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“…Double-strand breaks/cell/day generated by oxygen metabolism is 1000 times greater than the doublestrand breaks produced by this background radiation. The UNSCEAR 1994 Report [11] and recent studies [12,13] furnish extensive documentation of low-dose stimulation of many cellular functions including: antioxidant prevention ( Figure 2) [14] , enzymatic repair ( Figures 3 and 4) [15,16] , and immunologic and apoptotic removal ( Figure 5) [17] of DNA damage. This stimulation of each of these antimutagenic responses by low-dose radiation, in contrast to their suppression by high-dose radiation, predictably precludes a linear dose-response relation of radiation and health effects.…”

Section: The Antimutagenic Dna Damage-control Systemmentioning

confidence: 99%

Radiobiological Basis of Low-Dose Irradiation in Prevention and Therapy of Cancer

Pollycove¹

2007

Dose-Response

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ᮀ Antimutagenic DNA damage-control is the central component of the homeostatic control essential for survival. Over eons of time, this complex DNA damage-control system evolved to control the vast number of DNA alterations produced by reactive oxygen species (ROS), generated principally by leakage of free radicals from mitochondrial metabolism of oxygen. Aging, mortality and cancer mortality are generally accepted to be associated with stem cell accumulation of permanent alterations of DNA, i.e., the accumulation of mutations. In a young adult, living in a low LET background of 0.1 cGy/y, the antimutagenic system of prevention, repair and removal of DNA alterations reduces about one million DNA alterations/cell/d to about one mutation/cell/d. DNA alterations from background radiation produce about one additional mutation per 10 million cells/d. As mutations accumulate and gradually degrade the antimutagenic system, aging progresses at an increasing rate, mortality increases correspondingly, and cancer increases at about the fourth power of age. During the past three decades, genomic, cellular, animal and human data have shown that low-dose ionizing radiation, including acute doses up to 30 cGy, stimulates each component of the homeostatic antimutagenic control system of antioxidant prevention, enzymatic repair, and immunologic and apoptotic removal of DNA alterations. On the other hand, high-dose ionizing radiation suppresses each of these antimutagenic protective components. Populations living in high background radiation areas and nuclear workers with increased radiation exposure show lower mortality and decreased cancer mortality than the corresponding populations living in low background radiation areas and nuclear workers without increased radiation exposure. Both studies of cancer in animals and clinical trials of patients with cancer also show, with high statistical confidence, the beneficial effects of low-dose radiation.

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Radiation effects induced by low doses in complex tissue and their relation to cellular adaptive responses

Cited by 44 publications

References 19 publications

NF-κB-mediated adaptive resistance to ionizing radiation

NF-κB-mediated adaptive resistance to ionizing radiation

Abortive base-excision repair of radiation-induced clustered DNA lesions in Escherichia coli

Radiobiological Basis of Low-Dose Irradiation in Prevention and Therapy of Cancer

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