Long-Range Signal Transmission in Autocrine Relays

Přibyl, Michal; Muratov, Cyrill B.; Shvartsman, Stanislav Y.

doi:10.1016/s0006-3495(03)74906-6

Cited by 40 publications

(59 citation statements)

References 96 publications

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“…The range of the bystander signal in tissue, up to 1 mm, corresponds to Ϸ50-75 cell diameters. This surprisingly long range implies either that directly damaged cells produce long-range, diffusible bystander signals, perhaps through autocrine͞paracrine mechanisms (34)(35)(36)(37), or that a cell relay system is active, in which cells signal only their immediate neighbors (juxtacrine signaling), the signal being relayed by spatially intermediate, unirradiated bystander cells (38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away

Belyakov

Mitchell

Parikh

et al. 2005

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

271

166

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A central tenet in understanding the biological effects of ionizing radiation has been that the initially affected cells were directly damaged by the radiation. By contrast, evidence has emerged concerning ''bystander'' responses involving damage to nearby cells that were not themselves directly traversed by the radiation. These long-range effects are of interest both mechanistically and for assessing risks from low-dose exposures, where only a small proportion of cells are directly hit. Bystander effects have been observed largely by using single-cell in vitro systems that do not have realistic multicellular morphology; no studies have as yet been reported in three-dimensional, normal human tissue. Given that the bystander phenomenon must involve cell-to-cell interactions, the relevance of such single-cell in vitro studies is questionable, and thus the significance of bystander responses for human health has remained unclear. Here, we describe bystander responses in a three-dimensional, normal human-tissue system. Endpoints were induction of micronucleated and apoptotic cells. A charged-particle microbeam was used, allowing irradiation of cells in defined locations in the tissue yet guaranteeing that no cells located more than a few micrometers away receive any radiation exposure. Unirradiated cells up to 1 mm distant from irradiated cells showed a significant enhancement in effect over background, with an average increase in effect of 1.7-fold for micronuclei and 2.8-fold for apoptosis. The surprisingly long range of bystander signals in human tissue suggests that bystander responses may be important in extrapolating radiation risk estimates from epidemiologically accessible doses down to very low doses where nonhit bystander cells will predominate.bystander ͉ normal human tissue ͉ radiological risk

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Section: Discussionmentioning

confidence: 99%

Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away

Belyakov

Mitchell

Parikh

et al. 2005

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

271

166

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“…Spatially distributed excitable systems, or ''excitable media,'' are an important class of excitable systems whose main biological function is long-range signal transmission through self-sustained waves of activity (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). A canonical example of excitability is the ability of nerve cells to transmit pulses of electrical activity in the form of action potentials (4).…”

mentioning

confidence: 99%

“…Perhaps, the most well known example of excitable media in biology is the heart tissue, which relies on electrical couplings between excitable cells (2). On the other hand, many mechanisms of excitability exist in tissues that are mediated by different chemical messengers, notably, extracellular calcium (6,11), ATP (9), and peptide growth factors (7,10,12). In single-cell organisms, such as social amoeba Dictyostelium discoideum, excitability may arise as an emergent property of a large population of cells (5,13).…”

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confidence: 99%

Noise can play an organizing role for the recurrent dynamics in excitable media

Muratov

Vanden‐Eijnden

Weinan

2007

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

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We analyze patterns of recurrent activity in a prototypical model of an excitable medium in the presence of noise. Without noise, this model robustly predicts the existence of spiral waves as the only recurrent patterns in two dimensions. With small noise, however, we found that this model is also capable of generating coherent target patterns, another type of recurrent activity that is widely observed experimentally. These patterns remain essentially deterministic despite the presence of the noise, yet their existence is impossible without it. Their degree of coherence can also be made arbitrarily high for wide ranges of the parameters, which does not require fine-tuning. Our findings demonstrate the need to reexamine current modeling approaches to active biological media.stochastic resonance ͉ noise-induced coherence ͉ target patterns

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“…They are released into the medium by irradiated cells and can act in an autocrine, paracrine or long-range endocrine manner, depending on the context and on cell properties (e.g. receptor number on a cell surface) (18,(35)(36)(37)(38). The smallest molecules (those that are Ͻ1 kDa in molecular weight) can also migrate directly between neighboring cells through gap junctions (39,40).…”

Section: Molecules Involved In the Bystander Effectmentioning

confidence: 99%

Biophysical Models of Radiation Bystander Effects: 1. Spatial Effects in Three-Dimensional Tissues

Shuryak¹,

Sachs²,

Brenner³

2007

Radiation Research

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Non-targeted (bystander) effects of ionizing radiation are caused by intercellular signaling; they include production of DNA damage and alterations in cell fate (i.e. apoptosis, differentiation, senescence or proliferation). Biophysical models capable of quantifying these effects may improve cancer risk estimation at radiation doses below the epidemiological detection threshold. Understanding the spatial patterns of bystander responses is important, because it provides estimates of how many bystander cells are affected per irradiated cell. In a first approach to modeling of bystander spatial effects in a threedimensional artificial tissue, we assume the following: (1) The bystander phenomenon results from signaling molecules (S) that rapidly propagate from irradiated cells and decrease in concentration (exponentially in the case of planar symmetry) as distance increases. (2) These signals can convert cells to a long-lived epigenetically activated state, e.g. a state of oxidative stress; cells in this state are more prone to DNA damage and behavior alterations than normal and therefore exhibit an increased response (R) for many end points (e.g. apoptosis, differentiation, micronucleation). These assumptions are implemented by a mathematical formalism and computational algorithms. The model adequately describes data on bystander responses in the 3D system using a small number of adjustable parameters. ᭧

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Long-Range Signal Transmission in Autocrine Relays

Cited by 40 publications

References 96 publications

Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away

Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away

Noise can play an organizing role for the recurrent dynamics in excitable media

Biophysical Models of Radiation Bystander Effects: 1. Spatial Effects in Three-Dimensional Tissues

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