Ovarian failure and infertility are common side effects for women who undergo radiation and chemotherapy. In most mammals, the female's entire supply of oocytes is created during embryonic development, and as many as 80 percent of the oocytes die before birth. Oocytes that remain are extremely sensitive to agents used in cancer treatment, which trigger programmed cell death, a process known as apoptosis.
"Unfortunately, there are no pharmacological or other therapies to prevent this catastrophic problem," said Richard Kolesnick, M.D., head of MSKCC's Laboratory of Signal Transduction, and a lead author of the study.
Zvi Fuks, M.D., a collaborator and an expert on radiation effects, explained that women, from birth to menopause, are likely to become sterile if the ovaries are exposed to radiation during treatment for cancer.
Apoptosis begins in oocytes when a lipid termed ceramide is produced in response to radiation or drugs. S1P works by blocking ceramide action - the oocytes never receive the signal to begin apoptosis.
Two months after treating the female mice with radiation, the researchers mated them with normal males. Surprisingly, S1P-treated mothers delivered normal litters, and the offspring appeared normal by several criteria. Further, subsequent
Contact: Esther Carver
Memorial Sloan-Kettering Cancer Center