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Environmental Factor, October 2012

Extramural papers of the month

By Nancy Lamontagne

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Triclosan impairs heart and skeletal muscle contractility

NIEHS grantees report that triclosan hinders muscle contractions at a cellular level and also causes muscle problems in fish and mice. Triclosan is an antibacterial agent widely used in personal-care products such as hand soap and toothpaste, and it has been detected in waterways and fish. This new study provides evidence of the chemical’s potentially negative effects on human and environmental health and also reveals a mechanism for these effects.

The researchers evaluated the effects of triclosan on muscle cells. The triclosan interrupted normal communication between two proteins that function as calcium channels, causing skeletal and cardiac muscles to fail.

In animal studies, anesthetized mice had up to a 25-percent reduction in heart function measures within 20 minutes of exposure to the chemical. Mice given a single dose of triclosan showed an 18-percent reduction in grip strength for up to 60 minutes. The investigators also studied the effects of triclosan exposure on fathead minnows, a model organism used to study the effects of aquatic pollutants. Minnows exposed to triclosan in the water for seven days showed significantly reduced swimming activity compared to controls.

CitationCherednichenko G, Zhang R, Bannister RA, Timofeyev V, Li N, Fritsch EB, Feng W, Barrientos GC, Schebb NH, Hammock BD, Beam KG, Chiamvimonvat N, Pessah IN. 2012. Triclosan impairs excitation-contraction coupling and Ca2+ dynamics in striated muscle. Proc Natl Acad Sci U S A 109(35):14158-14163.

Pan-fried red meat increases risk for prostate cancer

An NIEHS grantee and her colleagues found that consuming more than 1.5 servings of pan-fried red meat per week is associated with an increased risk for prostate cancer. The findings point to carcinogens that accumulate in meats cooked at high temperatures as potential risk factors for prostate cancer.

The researchers examined data from nearly 2,000 men with and without prostate cancer. They looked at whether consuming various red meats, processed meats, and poultry was associated with an increased risk of prostate cancer. They took into account cooking methods, meat doneness, and estimated levels of carcinogens.

The study showed that men who consumed more than 1.5 servings of pan-fried red meat per week increased their risk of advanced prostate cancer by 30 percent, and eating 2.5 servings of red meat per week cooked at high temperatures increased risk 40 percent. Of the red meats studied, hamburgers, but not steak, were linked to an increased risk of prostate cancer, especially among Hispanic men. Men with diets high in baked poultry had a lower risk of advanced prostate cancer, while consumption of pan-fried poultry increased risk.

The researchers say that if future studies replicate their findings, then guidelines would be useful for helping the public understand how to cook meat in a way that reduces these carcinogens.

CitationJoshi AD, Corral R, Catsburg C, Lewinger JP, Koo J, John EM, Ingles S, Stern MC. 2012. Red meat and poultry, cooking practices, genetic susceptibility and risk of prostate cancer: results from the California Collaborative Prostate Cancer Study. Carcinogenesis; doi: 10.1093/carcin/bgs242 [Online 20 July 2012].

Uncovering a defective gene’s role in autism-type behaviors

A defective pten gene can lead to disruptions in the activity of neuronal mitochondria and autism-type behaviors in mice, according to a new study from NIEHS grantees. Pten is defective in some children with autism, and this new insight into how the gene affects the brain could lead to new drug targets.

To investigate the effects of a defective pten gene, the researchers studied mice with neurons containing only one copy of the gene, rather than the normal two. By four to six weeks after birth, the neurons of these mice showed malfunctioning mitochondria. At 20 to 29 weeks, the researchers observed a dramatic increase in DNA damage and mitochondrial dysfunction. The mice also began to avoid their littermates and engage in repetitive grooming, behaviors associated with autism. Mice with two copies of the pten gene did not have malfunctioning mitochondria or behavioral problems.

The researchers also found that defective pten interacted with the p53 gene to impair mitochondrial function in mice. This led to an increase in mitochondrial DNA damage and abnormal levels of energy production in the cerebellum and hippocampus, brain regions that are critical for social behavior and cognition.

CitationNapoli E, Ross-Inta C, Wong S, Hung C, Fujisawa Y, Sakaguchi D, Angelastro J, Omanska-Klusek A, Schoenfeld R, Giulivi C. 2012. Mitochondrial dysfunction in pten haplo-insufficient mice with social deficits and repetitive behavior: interplay between pten and p53. PLoS One 7(8):e42504; doi:10.1371/journal.pone.0042504 [Online 10 August 2012].

Infant exposure to specific molds linked with asthma risk

A new NIEHS-supported study provides evidence that infants exposed to three types of mold during infancy have an increased risk of developing asthma during childhood. Since the molds are commonly found in buildings that have water damage, the study shows the importance of quickly cleaning up water damage and mold in homes.

The researchers studied 289 infants who were part of the Cincinnati Childhood Allergy and Air Pollution Study. They collected house dust samples when the infants were 8 months old and analyzed the samples for 36 molds, endotoxin, house dust mite, cat, dog, and cockroach allergens. The researchers found that 25 percent of children whose parents had allergies were asthmatic by age 7 and that exposure to Aspergillus ochraceus, Aspergillus unguis, and Penicillium variabile was linked to asthma development in the high-risk study population.

CitationReponen T, Lockey J, Bernstein DI, Vesper SJ, Levin L, Khurana Hershey GK, Zheng S, Ryan P, Grinshpun SA, Villareal M, Lemasters G. 2012. Infant origins of childhood asthma associated with specific molds. J Allergy Clin Immunol 130(3):639-644.e5. Story Related Editorial

(Nancy Lamontagne is a science writer with MDB, Inc., a contractor for the NIEHS Division of Extramural Research and Training, Superfund Research Program, and Worker Education and Training Program.)

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