Blasting people with hard radiation � itself a carcinogen
� has never been a very elegant or attractive way to tackle
cancer. But it works, sometimes, and if a bit of radiation
can kill a few cells, then presumably a lot of radiation
can kill many cells. That, at least, has long been the
conventional wisdom. However, research sponsored by the
US National Cancer Institute suggests it may be time to
rethink how cells respond to radiation. The data was presented
on October 5 at the annual meeting of the American Society
for Therapeutic Radiology and Oncology in Atlanta, Georgia.
The new research shows that, although
low-level radiation has been deemed ineffective at killing
cancer in patients, it actually kills off more cancer
cells in lab cultures than doses that are 100 times
more powerful. The reason why provides insight into
how cancer can survive high-dose radiation, and may
pave the way to more effective radiotherapy in the future.
A protein called Ataxia Telangiectasia Mutated (ATM)
was identified as the culprit that protects cells �
cancerous or not � when they're under attack, which
is how the body perceives high levels of radiation.
The research was conducted at the
Johns Hopkins Kimmel Cancer Center. Investigators tested
a radiation dose 100 times lower than a high therapeutic
dose on cultured prostate and colon cancer cell lines.
Astonishingly, they found the low dose killed far more
cells.
Low-dose radiation killed 65% of
the cultured colon cancer cells, while high-dose radiation
killed just 40%. In addition, half of the prostate cancer
cells succumbed to low-dose radiation, compared to just
35% of those exposed to high radiation. The low-dose
radiation was spread over many days, an essential measure
because the amount emitted was just ten times higher
than normal background radiation.
This doesn't mean that hospitals
can now cure cancer patients while avoiding side effects,
simply by irradiating their patients' tumours at far
lower doses. What's important about the study is why
these cultured cell lines were so vulnerable to small
amounts of radiation.
"DNA repair is not foolproof �
it can lead to mistakes or mutations that are passed
down to other generations of cells," explains lead researcher
Dr Theodore DeWeese. "A dead cell is better than a mutant
cell, so if the damage is mild, cells die instead of
risking repair."
But when the radiation dose is
high, and massive DNA damage threatens to kill truly
large numbers of cells, the body goes into damage-limitation
mode. Dr DeWeese describes the defence mechanism as
"damage detection radar." What it does is switch on
the ATM protein, which attempts to repair DNA. Unfortunately,
when activated, the ATM protein acts to save all the
cells under attack - including the cancer cells.
The Johns Hopkins team believes
that in their experiment, low-dose radiation effectively
slipped in "under the radar" of the damage detection
system. They found that ATM activation in the cells
hit with low-dose radiation was about half of that found
in the heavily irradiated cell lines. When the team
reactivated the protein in the low-dose cell lines,
the cancer cells immediately began to fare better under
the radiation's assault, proving that ATM was the culprit
protecting them.
Clearly, this suggests that drugs
capable of blocking ATM activation around tumours could
greatly increase the cancer-killing power of standard
therapeutic radiation. "Tricking cancer cells into ignoring
the damage signals that appear on its radar could succeed
in making radiation more effective in wiping out the
disease," says Dr DeWeese.
That is the next step for the Johns
Hopkins researchers, who are currently studying ways
in which viruses could deliver ATM-blocking drugs to
cancer sites.
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