Exposure to a PAH before birth or via breast milk can lead to cancer.

Context

Childhood leukemia describes a family of diseases also known as blood cancers. There are at least four different types of leukemias and several different types of lymphomas. The type of leukemia or lymphoma is classified based on the type of blood cell that is causing the cancer.

In the United States, approximately 27% of all childhood cancers are leukemias. While leukemia survival has increased over the last 40 years, 22,000 people died from the disease in 2006 (National Cancer Institute 2006). Experts predicted an estimated 3,800 children (under the age of 20) would be diagnosed with leukemia in the United States in 2007, although exact figures are not yet available.

Treatment of new and recurrent cases of leukemia costs an estimated $2.6 billion dollars a year (Brown et al. 2002). This number does not include costs associated with job and/or productivity losses for patients and their families. If the total years of life lost to a malignancy are calculated, the societal impact of non-Hodgkin’s lymphoma (NHL; the fifth most common type of cancer), is greater than other cancers because of the disproportionate number of young people who die from the disease. Taking this life cost into account, NHL ranks as fourth among all malignancies in terms of economic impact in the U.S.

There is still a poor understanding of the underlying causes and risk factors associated with leukemia initiation and recurrence. Nevertheless, a growing body of evidence suggests that exposure to a variety of environmental factors particularly during the critical preconception and prenatal periods may be a contributing factor in increasing the risk for disease and disease recurrence (Birnbaum and Fenton 2003, Freedman et al. 2001, Meinert et al. 2000, Schüz et al. 2000; Shu et al. 1999, Stjernfeldt et al. 1986).

One class of environmental chemicals of growing concern in leukemia risk are polycyclic aromatic hydrocarbons (PAH). PAHs are found throughout the environment and are derived from incomplete burning processes. Sources include cigarette smoke, diesel exhaust and the industrial production of coke for making steel. Because PAHs are present in foods, a major route of exposure is via the diet (Luch 2005).

An estimated 11,000 metric tons of PAHs are released annually in the U.S. PAHs represent a “re-emerging” human health threat. Daily exposures from environmental sources are increasing, except for exposures from cigarette smoking, which has declined in the U.S. but remains prevalent in many other countries.

A major contributing factor to greater PAH exposure is the increasing need for energy - especially coal-based sources. An alarming expansion of the coal power industry is underway in China, now the largest consumer of coal in the world. Increased coal use in Asia affects U.S. citizens due to air currents carrying the contaminants across the Pacific Ocean. On any given day in the Los Angeles area, 25-33% of the atmospheric particulate matter (containing PAH) comes from China (Reisen and Arey 2005). The U.S. also obtains 50% of its energy from coal, and this percentage may increase as non-petroleum energy sources become increasingly important to the U.S. economy.
 

Dibenzo[a,l]pyrene (DBP) is the most potent PAH tested to date and is part of PAH mixtures found in the environment (Boström et al. 2002). DBP causes multi-organ cancer in many animals studied. It can cause lymphoma and cancers of the skin, endometrium, ovary, lung and liver (Boström et al. 2002, Buters et al. 2002, Higginbotham et al. 1993, Platt et al. 2004, Reddy et al. 1999a, Reddy et al. 1999b).

The authors' wanted to identify the critical time during development when  a common PAH called dibenzo[a,l]pyrene (DBP) causes lymphoma. This study follows earlier experiments that found mice exposed to DBP through their pregnant and nursing mothers developed highly aggressive lymphoma and lung cancer as adults. However, the scientists could not determine conclusively whether the detrimental PAH exposure occurred in the womb, while nursing or perhaps both.

The authors designed an elegant set of experiments where pregnant mice were given 15 mg/kg DBP during late pregnancy (day 17 of gestation) to replicate their earlier study. Once the baby mice were born, some were left with their birth mothers, and thus still possibly exposed to DBP through milk. A second group of mice were transferred to mouse foster mothers who had not been given DBP, so the pups would be nursing on DBP-free milk. A third set of mouse babies who had not been exposed to DBP in the womb, were fostered by mothers who had been exposed to DBP, so these pups would be drinking DBP-contaminated breast milk.

All of the pups, whether they were exposed to DBP prenatally, post-natally through lactation or both, were followed for 10 months and examined for signs of lymphoma (including distress, pain, death and tumors). 

Castro et al. found that late gestation was the most sensitive period for DBP exposure. Approximately 40% of the mice exposed to the chemical in the womb only died from complications associated with lymphoma and/or lung cancer. In comparison, more than 90% of the mice exposed to DBP only through their foster mother’s breast milk survived. Finally, in agreement with their earlier research, the authors found that DBP exposure both in the womb and while nursing was the most deadly, resulting in a 20% survival rate in the adult offspring 10 months later.