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Environmental Factor, November 2015

Extramural papers of the month

By Nancy Lamontagne

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Exposure to phenols affects pubertal development in girls

A new study finds that exposure to phenols, including some that are known to be endocrine disruptors, can affect the timing of puberty in girls. Early sexual maturation is associated with increased risk of breast cancer.

Although phenols are known to affect hormone activity, their effects on child reproductive development are not well studied. In the new study, researchers examined pubertal development among 1,239 girls who were enrolled in the Breast Cancer and the Environment Research Program Puberty Study when they were 6-8 years old. The girls, from three areas of the U.S., were followed annually for seven years to determine the age of first breast or pubic hair development. The researchers measured ten phenols in urine collected at enrollment.

The analysis revealed that girls with the highest levels of enterolactone and benzophenone-3 experienced breast development five to six months later compared to those with the lowest levels, with adjusted hazard ratios of 0.79 (0.64-0.98) and 0.80 (0.65-0.98), respectively. Breast development four to nine months earlier was observed for girls with the highest levels of triclosan and 2,5-dichlorophenol, with adjusted hazard ratios of 1.17 (0.96-1.43) and 1.37 (1.09-1.72), respectively.

The researchers suggested that benzophenone-3 and enterolactone may block production of the hormone androgen, and that triclosan and 2,5-dichlorophenol could affect thyroid hormones. Additional research is needed to confirm these findings and to identify any windows of susceptibility during which exposure might affect pubertal development.

CitationWolff MS, Teitelbaum SL, McGovern K, Pinney SM, Windham GC, Galvez M, Pajak A, Rybak M, Calafat AM, Kushi LH, Biro FM, Breast Cancer and Environment Research Program. 2015. Environmental phenols and pubertal development in girls. Environ Int 84:174-180.

Recombinase enzymes recognize matching DNA three bases at a time

The exchange of genetic information between DNA strands, known as DNA recombination, is important for DNA repair and also drives evolution. New research, funded in part by NIEHS, has revealed the physical basis for these DNA strand exchange reactions.

The study authors previously developed single-molecule methods to visualize DNA recombination, using an imaging technique known as total internal reflection fluorescence microscopy. Using this imaging approach and molecular dynamics simulation, they showed that members of the Rad51/RecA family of recombinase enzymes, which are responsible for DNA recombination, search for and recognize matching DNA strands three bases at a time.

The researchers studied four different recombinases — human Rad51, Escherichia coli RecA, eukaryotic forms of RecA, and Saccharomyces cerevisiae Dmc1. The imaging studies showed that bacterial RecA, the Rad51, and Dmc1 all stabilize intermediaries in the strand exchange in precise three nucleotide steps. They confirmed the finding using molecular dynamics simulation. Additionally, the researchers found that while Rad51, RecA, and Dmc1 can all step over DNA mismatches, only Dmc1, which is specialized for recombination during meiosis, can stabilize a mismatching triplet. This discovery provides insight into why eukaryotes evolved a recombinase that is specialized for meiosis.

CitationLee JY, Terakawa T, Qi Z, Steinfeld JB, Redding S, Kwon Y, Gaines WA, Zhao W, Sung P, Greene EC.. 2015. Base triplet stepping by the Rad51/RecA family of recombinases. Science 349(6251):977-981.

Time between births associated with autism risk

A new study, funded in part by NIEHS, found that second-born children, conceived either less than two years or more than six years after the arrival of their older sibling, have an increased risk of autism spectrum disorders. Unlike other studies, the new study ruled out other autism risk factors that might account for the findings.

Previous studies have linked both short and long pregnancy intervals with increased autism risk. To further investigate the link between interpregnancy length and autism, the researchers designed a study that controlled for some potentially confounding factors. Data for the study came from the electronic medical records of about 45,000 children born between 2000 and 2009 in Kaiser Permanente's Northern California hospitals.

Autism was diagnosed in 0.81 percent of second-born children born three to four years after their older sibling. For second-born children with interpregnancy intervals of less than six months, autism prevalence was 2.11 percent; for intervals of six to eight months, 1.74 percent; and for intervals of six years or more, 1.84 percent. The results could not be explained by maternal body mass index (BMI), change in BMI between pregnancies, parental age, maternal antidepressant medication use, or unfavorable events occurring during the first or second pregnancy.

The researchers said that future studies that incorporate maternal nutritional status,  especially folate and iron, and other factors, such as infertility, are necessary to understand the mechanisms involved in the association between autism and interpregnancy intervals.

CitationZerbo O, Yoshida C, Gunderson EP, Dorward K, Croen LA. 2015. Interpregnancy interval and risk of autism spectrum disorders. Pediatrics 136(4):651-657.

Faster measurements of brominated flame retardants

NIEHS grantees have developed a new method that can measure polybrominated diphenyl ether (PBDE) flame retardants and their analogs in human samples with a single 25-minute mass spectrometry analysis. The one-shot analysis technique would be cost-effective for large-scale studies examining the adverse health effects and accumulation patterns of brominated flame retardants.

PBDE flame retardants are commonly found in the environment and also accumulate in the human body. The hydroxylated (OH-BDE) and methoxylated (MeO-BDE) analogs of PBDEs are also of concern, because they accumulate in wildlife and humans. These forms naturally occur in the environment and can also result from biological transformation of manmade PBDEs. Typically, testing for flame retardants in human samples requires conversion of OH-BDEs into the more easily detectable MeO-BDEs. However, each compound must be measured separately, resulting in a series of time-consuming, expensive tests. To solve this problem, the researchers converted OH-BDEs into a similar, but alternate, compound allowing 12 PBDEs, 12 OH-BDEs, and 13 MeO-BDEs to be analyzed at once using gas chromatography with tandem mass spectrometry.

The researchers tested the method by measuring PBDEs and their analogs in paired human breast milk and serum samples from four people. Although the sample number was limited, the results showed different distribution profiles in serum and breast milk. The average concentrations of total PBDEs, OH-BDEs, and MeO-BDEs in breast milk were 59, 2.2, and 0.57 nanograms per gram of lipid, respectively. For serum, average concentrations were 79, 38, and 0.96 nanograms per gram of lipid, respectively.

CitationButryn DM, Gross MS, Chi LH, Schecter A, Olson JR, Aga DS. 2015. "One-shot" analysis of polybrominated diphenyl ethers and their hydroxylated and methoxylated analogs in human breast milk and serum using gas chromatography-tandem mass spectrometry. Anal Chim Acta 892:140-147.

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



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