http://www.ecanadanow.com/science/health/2006/11/30/common-cancer-drugs-could-be
-harmful-to-brain-cells/

Rochester (eCanadaNow) - Common drugs used to treat cancer may be more
harmful to healthy brain cells than the cancer cells that they are
intended to destroy. That is the conclusion of a study conducted by
researchers at the University of Rochester Medical Center and published
today in the Journal of Biology. The results, which also indicate that
chemotherapy may cause long-term brain damage, represent the closest
that scientists have come to pinpointing the underlying physiological
cause of "chemo brain," a common side effect of cancer treatment
that scientists are only now beginning to comprehend.

Cancer patients who receive chemotherapy have long complained of
adverse neurological side effects ranging from memory loss to, in
extreme cases, seizures, vision loss and even dementia. Until very
recently, these conditions were often dismissed as unrelated to the
cancer treatment and rather the result of the patient's mental state.
However, a growing body of evidence has documented the scope and
cognitive impact of chemo brain. A study earlier this year conducted by
the James P. Wilmot Cancer Center at the University of Rochester
suggested that upwards of 82% of cancer patients reported that they
suffer from some form of cognitive impairment.

While scientists have suspected that chemotherapy may have an impact on
healthy cells in the central nervous system, the precise mechanisms of
this condition were not fully understood. Now a University of Rochester
team led by Mark Noble, Ph.D. believes that they have unraveled the
mystery behind chemo brain. "This is the first study that puts chemo
brain on a sound scientific footing, in terms of neurobiology and
cellular biology."

As in other organs and systems in the body, the central nervous system
is populated with several types of cells that produce or repair the
cells needed for normal function. These cells fall into three general
categories: dividing stem cells, dividing intermediate cells types
called precursors and progenitors, and non-dividing mature cells.

Noble and his team exposed several different populations of healthy
brain cells as well as multiple human cancer cell lines to clinically
relevant levels of three commonly used chemotherapy drugs ?
carmustine, cisplatin, and cytosine arabinoside. These drugs are used
to treat a wide range of cancers, including certain types of breast
cancer, lung cancer, colon cancer, leukemia, Hodgkin and non-Hodgkin
lymphomas, and, in the case of carmustine, brain tumors.

They discovered that these drugs were far more toxic to the healthy
brain cells than to cancer cells; exposure levels typically used when
treating patients killed 70-100% of neural cells but just 40-80% of the
cancer cells. In animal models, several types of healthy cells
continued to die for at least six weeks after treatment. Notably, these
drugs were toxic to both non-dividing cells and dividing stem cells,
precursors, and progenitors even at very low concentrations.
Destruction of dividing cells was not altogether unexpected, as that is
what these drugs are designed to target. However, the loss of dividing
cells has onerous consequences as these populations are responsible for
replenishing the other cell types in the central nervous system.

Noble speculates that there are two possible ways the destruction of
these healthy cells result in cognitive problems. First, scientists
believe that the cell division ? or neurogenesis ? that occurs in
the hippocampus is essential to learning and memory. Hence, the
cognitive side effects of chemotherapy could potentially be traced to
the drugs' disruption of the process of neurogenesis in this
particular region of the brain.

Noble also points to the destruction of a specific cell type that plays
a critical supporting role in the central nervous system. These cells,
called oligodendrocytes, are responsible for producing myelin, the
fatty substance that, like insulation wrapped around a wire, covers
nearly all the large nerve cells processes ? called axons ? in our
bodies and helps signals in the nervous system move crisply and rapidly
from one point to another.

"The oligodendrocyte is an amazing cell that from its cell body
supports a volume of myelin membrane that can be thousands of times the
volume of the cell body," says Noble. "Myelin membranes are very
dynamic and are always being turned over and renewed. However, if you
kill the oligodendrocyte cell, then myelin membrane eventually
disintegrates."

Because everything in the nervous system is based upon precise timing
of information transfer, this destruction of the insulation necessary
in normal impulse transmission has significant neurological
ramifications.

Noble and his team are quick to point out that no one should avoid
cancer treatment because of these results and that chemotherapy will
remain a cornerstone of cancer therapy for the foreseeable future.
Instead, they believe that the opportunity for the scientific community
is to use this knowledge to develop ways to protect the brain's cells
from these drugs. Their research points to several potential strategies
that the Rochester scientists are now pursuing, ranging from
application of protective agents to understanding why some people are
spared neurological side effects while others are not. Additionally,
the approach used in the study could serve as a screening method to
analyze the effectiveness of new cancer therapies to determine, in
advance, which cell populations are at risk during treatment.

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Now they find this out!

TC