Drug protects fertility, offspring in mice after radiation exposure.(sphingosine 1-phosphate)(Brief Article)

2002 OCT 3 - (NewsRx.com & NewsRx.net) -- Scientists have discovered a drug that prevents sterility in female mice after exposure to ionizing radiation.

Additional findings suggest that this is accomplished without yielding genetic damage in the offspring of the irradiated mothers. Researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) and Massachusetts General Hospital, along with colleagues at other institutions, found that the compound sphingosine 1-phosphate (S1P) prevents the death of oocytes, or immature eggs, in the ovaries of female mice exposed to radiation, leaving more oocytes intact for reproduction. The research was published in the September 2002 issue of Nature Medicine.

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% 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, MD, head of MSKCC's Laboratory of Signal Transduction, and a lead author of the study.

Zvi Fuks, MD, 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 ...