Pregnancy spurs a tumor suppressor. (Science News of the week).

Women who undergo a full-term pregnancy at an early age are less likely to develop breast cancer than are women who never get pregnant. Scientists experimenting with rodents now have evidence that a cancer-fighting protein called p53 accounts for this protection.

The researchers propose that estrogen and progesterone, produced in abundance during pregnancy, alter breast cells in some fundamental way that enables them to produce ample p53 later in life. This girds cells against substances or various types of energy, such as radiation, that scramble DNA. These genetic rearrangements can start the cell proliferation that marks cancer.

Other researchers have suggested that pregnancy hormones make a woman's breasts more resistant to cancer because they cause breast cells to differentiate into new structures, including ducts to transport milk. This differentiation decreases the number of certain breast cells present in so-called terminal end buds, which some scientists suspect are susceptible to cancer.

Bert W. O'Malley and his colleagues at the Baylor College of Medicine in Houston conducted pregnancy-simulation experiments in which they gave young female rats and mice that hadn't ever been pregnant injections of estrogen and progesterone over several weeks. Other never-pregnant mice received an inert substance. The team also studied rodents that had given birth and nursed pups but received no injections.

When subsequently injected with cancer-causing chemicals, animals that had received hormones or had been pregnant responded by producing more p53 protein in breast cells than untreated animals did.

Ten days after exposure to a carcinogen, rodents that had received hormones or had been pregnant showed markedly less cell proliferation in the breast tissues than did animals that had received inert injections. Most of the study's results are slated to appear in the Oct. 23 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES.

Besides estrogen and progesterone, prolactin and various other hormones trigger the differentiation of mammary tissue during pregnancy. But drugs that stimulate prolactin failed in a past test to protect animals against carcinogens. To see whether p53 explains the difference, O'Malley and his colleagues induced prolactin production in some rats and then tested their cells for p53.

Breast cells in these animals showed no more p53 when exposed to carcinogens than did cells in animals getting a placebo. That suggests that it's the estrogen and progesterone in the hormone mix, not the presence of prolactin and its effects, that spur production of cancer-protective p53, say the researchers.

In other words, "differentiation doesn't explain the protection you get from pregnancy-hormone release," says Geoffrey L. Greene of the University of Chicago.

The p53 molecule switches various genes on and off, and the resulting chain of events probably brings about a form of suicide in cancer cells, which halts progression of the disease, says Lewis A. Chodosh of the University of Pennsylvania in Philadelphia. It may also halt the cell's normal cycle of growth and division. This freezing of the cell cycle would enable DNA damaged by carcinogens to be repaired by the cell's built-in maintenance machinery, Chodosh says.

The p53 protein isn't abundant in normal tissues. This study suggests that estrogen and progesterone released in pregnancy "activate a long-lasting p53 switch," says D. Joseph Jerry of the University of Massachusetts in Amherst. Still unclear is how the hormones perform this feat, says Jerry.