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Extramural Papers of the Month

By Jerry Phelps
March 2010

Obesity is a Tumor Promoter

Scientists at the University of California, San Diego confirm that obesity acts as tumor promoter in a recent publication in the prestigious journal Cell. Jointly funded by NIEHS and the Superfund Research Program, their study suggests that anti-inflammatory drugs taken routinely by millions of people may also reduce the risk of cancer in those at high risk due to obesity and other factors.

The research team found that liver cancer is promoted by a chronic inflammatory state that coincides with obesity. Liver cancer development was dependent on two well known inflammatory factors, IL-6 and tumor necrosis factor. These inflammatory cytokines caused liver inflammation and activation of an oncogenic transcription factor known as STAT3.

Mice prone to develop hepatocellular carcinoma were given a dose of a chemical carcinogen at two weeks of age and then divided into two groups - one on a regular, relatively low-fat diet and another on a high-fat diet. The mice on the high-fat diet developed more cancer. Additional studies using a strain of mice prone to obesity but fed a normal diet and given the same carcinogen, at the same age produced similar results.

Surprising results came in an experiment in which mice given the carcinogen at three months of age and fed a high fat diet developed cancers. Obese mice lacking receptors for either of the two cytokines did not show the same rise in liver cancer.

Citation: Park EJ, Lee JH, Yu GY, He G, Ali SR, Holzer RG, et al. (http://www.ncbi.nlm.nih.gov/pubmed/20141834?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=1)Exit NIEHS 2010. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 140(2):197-208.

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Phthalate Exposure Alters Children's Behavior and Cognitive Function

NIEHS-funded research from the Mount Sinai School of Medicine indicates that women with higher exposures to phthalates during pregnancy report more disruptive behaviors in their children. This study included 188 children whose mothers enrolled in the New York Children's Environmental Health Study. It is the first study evaluating the neurobehavioral development of older children in relation to their in utero phthalate exposure.

Phthalates are chemicals used to make plastics and are found in wide variety of consumer items including bottles, cosmetics, shampoo, lotions, and vinyl flooring. Ten phthalate metabolites were measured in the mothers' urine samples during the third trimester of pregnancy. When their children were 4 to 9 years old, the mothers were interviewed up to three times and completed a standard questionnaire to assess their children's behavior and cognitive abilities.

The results demonstrate that prenatal exposure to a group of phthalates commonly found in personal care products was significantly associated with poorer scores for aggression, conduct, and emotional control. There were no differences between boys and girls in the study and the associations were stronger as the level of phthalate exposure rose; however, few children's scores fell in the range of clinical significance. The results suggest the need for further research on the possible relationships between phthalate exposures and neurodevelopment and behavior.

Citation: Engel SM, Miodovnik A, Canfield RL, Zhu C, Silva MJ, Calafat AM, Wolff MS. (http://www.ncbi.nlm.nih.gov/pubmed/20106747?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=1)Exit NIEHS 2010. Prenatal Phthalate Exposure is Associated with Childhood Behavior and Executive Functioning. Environ Health Perspect. Jan. 8 [Epub ahead of print]

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Asthma Symptoms in Children Associated with Acetaminophen Use During Pregnancy

Children whose mothers took acetaminophen while pregnant are more likely to have persistent symptoms of asthma at age five according to a new NIEHS-funded study by researchers at the Columbia Center for Children's Environmental Health involving 300 African-American and Dominican Republic children living in New York City.

The study found that the relationship was stronger in a subset of children with a variant gene for glutathione S transferase, an enzyme involved in the detoxification of foreign substances in the body. This result suggests that less efficient detoxification may be the link between acetaminophen and asthma.

The researchers found that children of mothers reporting acetaminophen use during pregnancy were more likely to wheeze, visit an emergency room for respiratory problems, and develop allergic symptoms than children whose mothers did not take the common analgesic, with effects diminishing as the children aged.

Acetaminophen use among children in the U.S. has increased dramatically since the early 1980's, possibly due in part to the discovery of the association between aspirin use and Reye's syndrome in children. This rise coincides with the increase of asthma diagnoses. The findings in the current study provide a possible explanation for the rise in asthma, especially in minority populations, and suggest caution for the use of acetaminophen during pregnancy.

Citation: Perzanowski MS, Miller RL, Tang D, Ali D, Garfinkel RS, Chew GL, et al. (http://www.ncbi.nlm.nih.gov/pubmed/19850963?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=5)Exit NIEHS 2010. Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban low-income cohort. Thorax (2):118-23.

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PCBs Found in Indiana Harbor

University of Iowa researchers supported by the Superfund Research Program report finding polychlorinated biphenyls (PCBs) in sediments of the Indiana Harbor and Ship Canal in East Chicago, Ind., which is scheduled to be dredged in the near future.

The canal is part of the Calumet River that flows out of Lake Michigan. Scientists and policy makers aren't sure whether dredging will help the estuary by removing the PCBs from past industrial discharge or hurt the environment by stirring them up.

PCBs are a class of organic compounds that were used for decades in many applications including electrical transformers, capacitors, and coolants. The U.S. Congress banned all uses of PCBs in 1979, but because of their stable chemical structure and persistence, their presence in water and sediments continues to be a source of contamination for fish, wildlife, and humans. PCBs are known to cause a wide variety of adverse health effects including cancer, immune dysfunction, neurodevelopmental disorders in children, and other effects associated with endocrine disruption.

The dredging project will remove the sediment from the canal and dispose of it nearby in a confined disposal facility. The project provides a unique opportunity to study the effectiveness of the project and will provide insights for the cleanup of other contaminated sites.

Citation: Martinez A, Wang K, Hornbuckle KC. (http://www.ncbi.nlm.nih.gov/pubmed/20131898?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=1)Exit NIEHS 2010. Fate of PCB Congeners in an Industrial Harbor of Lake Michigan (dagger). Environ Sci Technol. Feb 4 [Epub ahead of print].

(Jerry Phelps is a program analyst in the NIEHS Division of Extramural Research and Training.)



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