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BYSTANDERS, ADAPTIVE RESPONSES AND GENOMIC INSTABILITY - POTENTIAL MODIFIERS OF LOW-DOSE CANCER RESPONSES.
Citation:
Preston, R J. BYSTANDERS, ADAPTIVE RESPONSES AND GENOMIC INSTABILITY - POTENTIAL MODIFIERS OF LOW-DOSE CANCER RESPONSES. . Presented at Society of Toxicology 42nd. Annual Meeting, Salt Lake City, Utah, March 9-13, 2003.
Description:
Bystanders, Adaptive Responses and Genomic Instability -Potential Modifiers ofLow-Dose
Cancer Responses
.
There has been a concerted effort in the field of radiation biology to better understand cellular
responses that could have an impact on the estin1ation of cancer risk (and possibly other health risks) at low dose levels. It is unclear which of these responses are produced ftom chemical exposures.
Bystander effects are described as a response in cells that are known not have been traversed by a particle track. Low LET responses have been described. Such responses include induction of gene expression, mutagenic responses and cell transformation. Thus, the concept of effects only in "hit" cells does not hold and cells at risk per unit dose takes on a new definition. The bystander effects are the result of different cellular processes; cell-cell communication and diffusion mediated effects.
Adaptive responses for a variety of cellular endpoints have been described for radiation and
chemical exposures. The actual response is lower when a small adaptive dose is given prior to a much larger challenge dose than when the challenge dose alone is given. Thus, there is reduction of response per unit dose under adaptive conditions. However, adaptive responses are not universal and there is considerable interindividual variation.
A number of studies have shown that genomic instability can occur at times quite far removed
from a radiation exposure. This process also calls into question the concept of response per unit dose. Genomic instability is a hallmark of most tumor types. It remains to be established if it is induced or selected by exposure to radiation or chemicals.
Adaptive responses and genomic instability can be induced in bystander cells. This further
complicates the considerations of dose and response. There is the potential for all these cellular responses to modify the dose response for cancer at low exposure levels. The need is to further study the underlying mechanisms for these responses for radiation and to establish if similar effects can be operative for chemical exposures.
(This is an abstract of a proposed presentation and does not necessarily reflect EP A policy.)