Radiation Hormesis: Data and Interpretations

Upton, Arthur C.

doi:10.1080/20014091111956

Cited by 85 publications

(38 citation statements)

References 64 publications

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“…of astronauts during long-term space flights, risk assessment and management, and cancer treatment strategies (Delone et al, 1991;Wang and Cai, 2000;Upton, 2001;Takahashi et al, 2002;Bonner, 2003;Mortazavi et al, 2003aMortazavi et al, , 2003bLiu, 2003;Schaffer et al, 2004;Preston, 2005). In preliminary cytogenetic studies, after in vitro irradiation with a test dose of gamma rays, a strong cytogenetic AR was induced in the lymphocytes of residents of the very high background radiation areas of Ramsar (Ghiassi-nejad et al, 2002).…”

Section: Relevance Of the Adaptive Responsementioning

confidence: 99%

“…adaptive protection causing DNA damage prevention and repair and immune stimulation (Upton , 2001;Liu, 2003;Ghiassi-nejad et al, 2004;Feinendegen, 2005). Low to intermediate doses of ionizing radiation have been observed to enhance growth and survival, augment the immune response, and increase resistance to the mutagenic and clastogenic effects of further irradiation in plants, bacteria, insects and mammals (Upton, 2001).…”

Section: Relevance Of the Adaptive Responsementioning

confidence: 99%

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Adaptive response: some underlying mechanisms and open questions

2008

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Organisms are affected by different DNA damaging agents naturally present in the environment or released as a result of human activity. Many defense mechanisms have evolved in organisms to minimize genotoxic damage. One of them is induced radioresistance or adaptive response. The adaptive response could be considered as a nonspecific phenomenon in which exposure to minimal stress could result in increased resistance to higher levels of the same or to other types of stress some hours later. A better understanding of the molecular mechanism underlying the adaptive response may lead to an improvement of cancer treatment, risk assessment and risk management strategies, radiation protection, e.g. of astronauts during long-term space flights. In this mini-review we discuss some open questions and the probable underlying mechanisms involved in adaptive response: the transcription of many genes and the activation of numerous signaling pathways that trigger cell defenses -DNA repair systems, induction of proteins synthesis, enhanced detoxification of free radicals and antioxidant production.

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Section: Relevance Of the Adaptive Responsementioning

confidence: 99%

Section: Relevance Of the Adaptive Responsementioning

confidence: 99%

Adaptive response: some underlying mechanisms and open questions

2008

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“…10 And reduction of ROS by antioxidants can shorten life span. 10,53 It has even been suggested that the beneficial effects of physical exercise are partly based on the ROS generating capability of exercise. 10 If induction of ROS prolongs life span (by whatever mechanism), then ROS simply cannot be a cause of aging.…”

Section: Paradoxical Effects Of Ros: Hormesismentioning

confidence: 99%

Aging: ROS or TOR

2008

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It is widely believed that aging is caused by the accumulation of random molecular damage due to reactive oxygen species (ROS). Here I discuss evidence for and against the ROS theory. Remarkably, even supporting evidence has an alternative explanation, consistent with the model that aging is driven by the TOR (target of rapamycin) signaling pathway. PrologueThis article may seem provocative because it presents a novel point of view on aging. It discusses that aging is not the life-long accumulation of molecular damage, is not decline and is not caused by reactive oxygen species (ROS). And data that support the ROS theory have an alternative explanation. The article suggests that aging is a consequence of over-activation of growth-promoting signaling pathways such as the TOR (target of rapamycin; also known in mammals as mTOR) pathway. Of course, ROS induce molecular damage. However, ROS-induced molecular damage is not lifelimiting, simply because the TOR-driven aging terminates life first. Therefore, TOR (mTOR) cannot be incorporated into the ROS theory. But ROS, which play a signaling role in the TOR pathway, can be incorporated into the TOR model. Some opponents have called this point of view extreme, one-sided and unbalanced. But a model is either correct or incorrect. If the article were "less extreme", thus allowing TOR to be incorporated into the ROS model, then it would be plainly wrong. It would be a completely different model, with aging seen as decline, not as hyperfunction.The TOR-centric model resolves paradoxes of aging. 1 It is believed that aging is extremely multifactorial and complex and that all contradictions just illuminate its complexity. From the TOR perspective, the complexity is turning out to be simplicity. 1 But this article is not about a new theory of aging. A general outline of the theory was published in 2006. 2 This article has a special focus: TOR or ROS. In particular, it discusses how the same data that support the ROS model can be explained by the TOR model. Most importantly, this may have tremendous clinical applications to prevent age-related blindness and memory loss, cancer and stroke, for instance, given the existence of prescription drugs that inhibit TOR. 3,4

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“…Risk estimates at or below these levels are difficult to obtain directly from epidemiological data (8) and are based, at least partly, on linear extrapolations from existing high-dose data (9)(10)(11). However, the validity of this assumption is challenged by some radiobiological phenomena, such as the bystander effect, low-dose hypersensitivity, delayed genomic instability, and induced DNA repair, which are difficult to reconcile with a linear no-threshold hypothesis based on mechanistic considerations (12)(13)(14)(15)(16)(17). Because these effects have yet been demonstrated only in cell culture systems or, at best, in animal models, their in vivo significance for people has remained unclear.…”

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confidence: 99%

In vivo formation and repair of DNA double-strand breaks after computed tomography examinations

Löbrich

Rief

Kühne

et al. 2005

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

384

342

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Ionizing radiation can lead to a variety of deleterious effects in humans, most importantly to the induction of cancer. DNA doublestrand breaks (DSBs) are among the most significant genetic lesions introduced by ionizing radiation that can initiate carcinogenesis. We have enumerated ␥-H2AX foci as a measure for DSBs in lymphocytes from individuals undergoing computed tomography examination of the thorax and͞or the abdomen. The number of DSBs induced by computed tomography examination was found to depend linearly on the dose-length product, a radiodiagnostic unit that is proportional to both the local dose delivered and the length of the body exposed. Analysis of lymphocytes sampled up to 1 day postirradiation provided kinetics for the in vivo loss of ␥-H2AX foci that correlated with DSB repair. Interestingly, in contrast to results obtained in vitro, normal individuals repair DSBs to background levels. A patient who had previously shown severe side effects after radiotherapy displayed levels of ␥-H2AX foci at various sampling times postirradiation that were several times higher than those of normal individuals. ␥-H2AX and pulsed-field gel electrophoresis analysis of fibroblasts obtained from this patient confirmed a substantial DSB repair defect. Additionally, these fibroblasts showed significant in vitro radiosensitivity. These data show that the in vivo induction and repair of DSBs can be assessed in individuals exposed to low radiation doses, adding a further dimension to DSB repair studies and providing the opportunity to identify repair-compromised individuals after diagnostic irradiation procedures.␥-H2AX foci ͉ ionizing radiation ͉ low radiation doses ͉ radiosensitivity ͉ blood lymphocytes I onizing radiation (IR) exposure is frequently encountered in a person's life. Sources of natural radiation include cosmic rays that come from outer space and the sun and radioactive substances that exist in earth and inside the human body. In addition to occupational exposure, flights at high altitude, manned space exploration, and radiological terrorism represent significant sources of radiation risk for part of the population. Diagnostic x-ray procedures including screening tests for cancer are the largest man-made source of radiation exposure, accounting for Ϸ14% of the total exposure level worldwide (1-4).Exposure to IR can induce leukemia and other cancers. It is assumed that damage to DNA in the nucleus of a single cell can initiate carcinogenesis. Among the different types of lesions induced, DNA double-strand breaks (DSBs) are considered to be the most relevant of the deleterious effects of IR (5, 6). Remarkably, even a single radiation track and, hence, the smallest possible quantity of IR can produce this kind of damage. Estimates of cancer risk from exposure to IR are based on epidemiological studies of exposed human populations, especially the atomic bomb survivors of Hiroshima and Nagasaki. These studies have provided relatively reliable estimates of risk for moderate to high doses (1, 2). The lowest dose...

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Radiation Hormesis: Data and Interpretations

Cited by 85 publications

References 64 publications

Adaptive response: some underlying mechanisms and open questions

Adaptive response: some underlying mechanisms and open questions

Aging: ROS or TOR

In vivo formation and repair of DNA double-strand breaks after computed tomography examinations

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