Bystander radiation effects studied in vivo in mice

Published in The Hindu on October 2, 2008

In the first ever proof-of-principle demonstration done in vivo, scientists have shown that cells that are not directly exposed to radiation can initiate tumour development. The experiments were done on mice.

This study challenges the central dogma of radiation biology — biological effects of ionizing radiation are a direct consequence of DNA damage occurring in irradiated cells.

Though the dogma has been challenged during the last two decades, most of the studies done were restricted to cell-cultures. This is the first study done in-vivo to understand how even cells not exposed to radiation can become cancerous.

The paper was published in a recent issue of the journal Proceedings of the National Academy of Sciences (PNAS).

The version challenging the dogma states that genetic/epigenetic changes do occur even in cells that are unexposed to radiation but which are in the immediate neighbourhood of the irradiated cells.

Bystander cells

These cells are called the ‘bystander cells.’ The changes occur due to cell-to-cell communication or soluble factors released by the irradiated cells.

Radiosensitive Patched-1 (Ptch1) heterozygous mice were chosen for the study. The heads of the mice were first shielded using lead before their whole bodies were exposed to X-ray radiation. Since lead is an effective shielding material, the brain cells should have ideally shown no damage. That was not the case, though.

A particular kind of tumour of the brain called medulloblastoma was seen in the experimental animals.

But it should be mentioned that the amount of X-ray that can be shielded by lead depends directly on the thickness of the lead used.

“The individual shields used were 4-mm thick,” noted Dr. Anna Saran in an email to this Correspondent. Dr. Saran of the Biotechnology Unit, ENEA CR Casaccia, Rome, Italy, is one of the authors of the paper.

And apart from the attenuated radiation, the shielded tissues also received scattered radiation that was deflected from irradiated tissues.

Another cohort

The total X-radiation due to attenuation and scattering was calculated as 0.036 Gy (1.2 per cent of the total dose to the shielded tissues). So Dr. Saran and other researchers subjected another set of mice to 0.036 Gy radiation to study the effects of such radiation on brain tissues.

All the mice exposed to 0.036 Gy should have also shown similar radiation induced tumour as seen in the brain tissues of the lead shielded mice. That was not the case, though. No signs of disease above background level were seen in the control group at 31 weeks, which is the time when tumour due to radiation manifests in the cerebellum, notes the paper.

But since the 0.036 Gy was given from a distance to the control group, is it right to compare the findings of the two groups?

“The shielded mice suffered much more damage than mice receiving the scatter dose directly. This means their brains received additional radiation damage from irradiated tissues,” Dr. Saran noted.

Other results also showed that damage due to bystander radiation was significant. They also found that inhibiting the cell-cell communication reduced the bystander radiation effect.

Relevance to humans

So what does this study mean for humans? A particular mutation makes humans susceptible to cancer and high radiosensitivity. However, the presence of the mutant alleles is low in humans.

“But if at low radiation doses, bystander as well as irradiated cells can also be induced to become malignant, low levels of radiation could be more hazardous than we currently believe,” Dr. Saran noted.

But calling for a reduction in the dose currently used for clinical diagnosis cannot be done based on this study. “The effect should be proven at lower doses,” cautioned Dr. Saran. 3 Gy dose is never used for diagnosis.

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