LINUS PAULING INSTITUTE RESEARCH REPORT

Photo of David Williams

Can the Maternal Diet During Pregnancy Protect the Fetus from Cancer and Birth Defects?

David E. Williams, Ph.D.
Professor of Environmental and Molecular Toxicology

Chemoprevention of cancer by dietary strategies is a major focus of research in the Linus Pauling Institute and has been the subject of a number of articles in past LPI Newsletters. Approximately one third of all cancers are related to diet, and many vitamins, minerals, and phytochemicals (plant chemicals) provide protection against chemically-induced or spontaneous cancers. Cancer chemoprevention could potentially save thousands of lives and millions of dollars in health-care costs every year.

My laboratory group has recently begun to study the potential of phytochemicals to protect a very susceptible population, the developing fetus, from the effects of exposure to toxic chemicals, including carcinogens and teratogens (chemicals that cause birth defects).

Fetal chemical exposure and childhood cancers

In the U.S., cancer is the leading cause of death in children from 1 to 20 years of age, accounting for more deaths than asthma, diabetes, cystic fibrosis, and AIDS combined. This year, 12,500 children will be diagnosed with cancer and 2,300 will die from cancer.

The EPA lists over 70,000 synthetic chemicals to which we are exposed to varying degrees depending upon our occupation, lifestyle, and intake of prescription or recreational drugs. Some of these chemicals, including chlorinated hydrocarbons like DDT, polychlorinated biphenyls (PCBs), and dioxin, are present in women’s fat tissue and in the milk of lactating mothers. This means that these chemicals are available to both the fetus and infant.

Certain environmental exposures to the human fetus in utero are highly correlated with an elevated risk of developing cancer. For example, there is strong evidence that maternal exposure to ionizing radiation is associated with the development of childhood leukemia. Maternal use of the therapeutic drug diethylstilbestrol is linked to the development of a rare vaginal cancer in female offspring. Exposure to many other chemicals, such as paints, petroleum products, solvents, pesticides, and metals, has also been correlated, although inconclusively, with elevated risk of childhood cancer. A recent estimate puts the percentage of all childhood cancers caused by environmental chemical exposures at about 5%.

Results from animal studies have added to the concern over fetal exposure to carcinogens. For example, offspring born to pregnant mice exposed to polycyclic aromatic hydrocarbons (PAHs, produced by the burning of organic material) develop cancers of the lung, liver, and skin.

Fetal chemical exposure and birth defects

Each year, approximately 150,000 babies in the U.S. are born with major birth defects, and an additional 14 to 22% of babies are born with minor developmental defects. Birth defects are the leading cause of infant mortality, and the infant mortality rate in the U.S. is higher than in 26 other nations. It is estimated that 3% of birth defects result from maternal exposure to teratogens. In addition, teratogens may play a role in the high rate of miscarriages, which may be as high as 50% of recognized and unrecognized pregnancies. Fetal exposure to the class of chemicals known asendocrine disruptors is believed to have potentially adverse effects on normal development and reproduction in offspring.

David Williams working in the laboratoryChemicals known to be human teratogens include the infamous thalidomide, the anticonvulsant drug phenytoin (Dilantin), retinoids, dioxin, cocaine, and alcohol. Thalidomide was developed in the late 1950s as an anti-nausea drug to treat symptoms of morning sickness. While awaiting approval for its release in the U.S., evidence appeared that babies born to women in Europe taking thalidomide exhibited a high rate of serious birth defects, including the absence of limbs and shortened long bones of the limbs. The European evidence prevented the introduction of thalidomide in the U.S. The case of thalidomide is often cited as an example of the ineffectiveness of animal testing for human toxicity because exposed animals did not exhibit serious problems. However, it can be argued that this was actually a case of insufficient testing. We now know that only a few strains of rabbits and primates are sensitive to the teratogenic effects of thalidomide and then only during a short period of the pregnancy. What we learned about thalidomide led to significant changes in FDA requirements for drug approval.

Exposure to some teratogens, such as alcohol, cocaine, and prescription drugs, during pregnancy can be reduced or eliminated, but exposure to others like dioxin that are widespread in the environment is much more difficult to eliminate. In the case of epileptics who depend on phenytoin to control seizures, alternative drugs need to be considered during pregnancy in order to protect the fetus.

Many of these teratogens appear to act by initiating oxidative damage to critical cellular targets in the developing organism. This suggests that dietary antioxidants should be capable of providing protection against teratogens.

The importance of good maternal prenatal nutrition has long been recognized. We have learned that the risk of neural tube defects (spina bifida) can be dramatically reduced with folate supplementation. Can we provide protection against chemical carcinogenesis and teratogenesis by maternal supplementation with other micronutrients and phytochemicals?

New research

As part of a multi-investigator grant from the National Cancer Institute, my laboratory, along with the other faculty of the LPI Cancer Chemoprotection Program, Drs. George Bailey and Rod Dashwood, will begin studies to assess the efficacy of phytochemicals in the maternal diet in preventing transplacental carcinogenesis. In one study, pregnant mice will be fed diets containing various levels of indole-3-carbinol, which is a major phytochemical from cruciferous vegetables; green and white tea; or chlorophyllin, a water-soluble derivative of the green plant pigment, chlorophyll, used for many years in humans for wound healing and the reduction of body odors. These substances will be fed before and during oral exposure to dibenzo[a,l]pyrene (DBP). DBP is a PAH present in the environment from sources like tobacco smoke and charcoal-broiled meats. Maternal exposure to DBP produces high rates of lung cancer in offspring about one year after birth. This model is relevant to humans for several reasons. First, the human fetus exhibits markedly enhanced susceptibility to DNA damage induced by transplacental PAH. Second, in non-smokers, diet accounts for approximately 70% of total PAH exposure. Third, a significant portion of the total lifetime exposure to PAHs, PCBs, and dioxin occurs transplacentally and through breast feeding.

Indole-3-carbinol and tea polyphenols may provide protection against PAH carcinogenesis by affecting maternal and/or fetal enzymes that metabolize the carcinogen or by acting as general antioxidants. Chlorophyllin may act by binding with PAHs andpreventing them from reaching the fetus. Our results should allow us to develop an under-standing of these possible mechanisms. Eventually, we hope that these studies will result in dietary recommendations for pregnant women that reduce the risk of harm to the fetus from exposure to ubiquitous environmental chemicals.

Last updated May, 2003


Micronutrient Research for Optimum Health


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