2002 ASCB Annual Meeting Press Book - page 11

December 14-18, 2002, San Francisco, CA
Safe from Harm: A New
Agent to Protect Fertility
During Cancer Therapy
Chemotherapy and radiotherapy are strong medicine but
they can be harsh treatment. Along with a cancer diagnosis, a
female patient must also face the possibility of infertility and
premature menopause. For a girl or a woman of reproductive
age, a routine side effect of these common anti-cancer treat-
ments is the inadvertent destruction of the eggs stored in her
ovaries since birth.
The American Cancer Society estimates that one in 52
females younger than 40 (
., the years when their fertility is
vulnerable) will be diagnosed with cancer. Although some will
be cured by surgery, the vast majority of these young girls and
women will receive chemotherapy, radiation or a combination
of the two. For the past five years, a major collaborative effort
between the laboratory of Jon Tilly at the Massachusetts Gen-
eral Hospital in Boston and groups headed by Richard
Kolesnick and Zvi Fuks at Memorial Sloan-Kettering Cancer
Center in New York to find an agent that would protect the
ovaries from the ravages of anti-cancer therapies has centered
on sphingosine-1-phosphate (S1P). In major studies published
Nature Medicine
in 1997 and 2000, the collaborators showed
that when this fatty chemical produced naturally in the body
was injected into female mice, it could protect their eggs from
the lethal effects of radiotherapy, and potentially chemo-
therapy. Now comes a vital test of the protective effects of
S1P; whether the eggs protected by S1P would be fertile and
whether oocytes derived with S1P-protected eggs would have
levels of genetic damage that would endanger the health or
fertility of any offspring that resulted. The results, which are
also published in
Nature Medicine
, are promising.
To assess S1P’s impact on genetic stability, Kolesnick
led a multi-institutional team of researchers in a study of DNA
damage in three generations of female mice, irradiating the
first generation to compare S1P-treated females to untreated
females, and both groups to non-irradiated controls. The stud-
ies showed the fertility of the unprotected but irradiated fe-
males falling by as much as 85%. Those protected by S1P
maintained normal fertility throughout their adult lives. Sec-
ondly, a screening of nearly 500 first- and second-generation
offspring conceived by these protected females found no evi-
dence of genetic damage or defects.
To measure potential DNA damage, eggs from S1P-pro-
tected females were closely examined for breaks in chromosomes
or inappropriate recombination events between chromosomes that
should not normally pair with each other, both important signs of
DNA damage. None were seen. The scientists also looked to see
if there were any signs of genetic damage in other cells in the
first-and second-generation offspring, by looking for fragmented
chromosomes in blood cells. The offspring of the S1P-treated
mothers did not show any increased signs of damage.
Taken with the previous studies, Kolesnick and col-
leagues—Jon Tilly and Gloria Perez at Harvard Medical School,
Fuks at Sloan-Kettering, William Morgan at the University of
Maryland, Baltimore, and Pat Hunt at Case Western Reserve in
Cleveland—believe this new report is critical evidence that S1P
might be capable of preserving ovarian function during cancer
therapy without causing genetic mayhem afterward.
Contact: Richard N. Kolesnick, Memorial Sloan-Kettering
Cancer Center, Pharmacology, 1275 York Ave, New York, NY
10021, (212) 639-7558,
Sphingosine 1-phosphate Preserves Fertility in Irradiated Fe-
male Mice Without Propagating Genetic Damage in Offspring.
R. N. Kolesnick,
F. Paris,
G. I. Perez,
Z. Fuks,
A. Haimovitz-
M. Bose,
A. Ilagan,
P. Hunt,
W. Morgan,
J. L.
Pharmacology, Memorial Sloan-Kettering Cancer
Center, New York, NY,
Obstetrics and Gynecology, Harvard
Medical School, Boston, MA,
Radiation Oncology, Memo-
rial Sloan-Kettering Cancer Center, New York, NY,
tion Oncology, University of Maryland, Baltimore, MD,
netics, Case Western Reserve, Cleveland, OH
At the ASCB Meeting: Presentation 819, Minisymposium
13: Apoptosis and Cellular Senescence. Author presents:
Monday, December 16, 4:25 —4:45 PM.
Moria et al.,
Nature Medicine,
6:1109-1114, 2000
Reprinted with permission of Nature Publishing Group.
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