The Bystander Effect: The Potential Ripple Effect of Cancer Radiation

It was previously thought that the adverse effects of radiation, one of the only legally sanctioned standards of care for cancer patients, were due only to the damage incurred by genetic material secondary to energy deposition of ionizing radiation (1). This notion, however, was refuted by evidence that healthy cells exhibit the effects of radiation exposure when transferred to a medium in which irradiated cells were incubated (2) or when they merely reside in the same vicinity of previously irradiated cells (3), and that patients administered radiotherapy show abscopal effects, or the effects of radiotherapy even in organs distant from the site of radiation (4, 5, 6).

Adding to this body of literature is that clastogenic, or chromosomal-damaging factors, are produced in tissues or cell cultures that were not directly irradiated upon exposure to irradiated serum (7, 8). Accompanying this discovery is the insight that so-called bystander information is conveyed from irradiated to un-irradiated cells, tissues, and animals such as bullfrog tadpoles, rainbow trout, medaka, fathead minnow, zebrafish, and mice (9, 10, 11, 12, 13, 14, 15, 16). In some of these experiments, fish that are directly irradiated, for instance, liberate signals that are communicated to and affect non-irradiated fish (11, 12, 13, 14). Similarly, signals secreted by irradiated mice have been illustrated to incite immunosuppression in non-irradiated mice (10).

In one experiment, radiation-naive rodents placed in the same cage with rodents that had previously received a single dose of ionizing radiation to one brain hemisphere revealed that similar or even greater effects were observed in the cage mates relative to the irradiated rats, illuminating that signal transmission occurred between two live animals (1). Despite radiation of an isolated brain hemisphere, release of bystander signals occurred from both cerebral hemispheres as well as a remote organ, the bladder, which altered the physiological response in non-irradiated cells (1).

Most frightening were experiments where irradiated rats translated bystander factors to un-irradiated rats, which incited signal production in both the brain and bladder of the un-irradiated animals that merely shared a cage with irradiated animals for two days (1). The researchers in fact conclude, “Our results support the hypothesis that proximity to an irradiated animal induces signaling changes in an unirradiated partner…the results could have implications for caregivers and hospital staff treating radiotherapy patients” (1, p. 72).

When mammals are dosed with radiation equivalent to or exceeding doses of 4 grays, their un-irradiated cage mates exhibit various adverse effects, including leukopenia, or decreased numbers of white blood cells, which predisposes individuals to infection, alongside other markers of immune suppression and chromosomal damage (1, 17). This research may suggest adverse health effects for medical practitioners and family in close proximity to cancer patients receiving radiation.

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