Extramural papers of the month
By Nancy Lamontagne
- Silicone wristbands as personal passive samplers
- Exposure to bisphenol A linked with early-onset prostate cancer
- Possible new autoimmune disease treatment without side effects
- Methylation in the adult mammalian brain
Silicone wristbands as personal passive samplers
NIEHS-funded investigators report that commercially available silicone wristbands could be modified for use as a personal passive sampling device, turning them into a valuable and easy-to-use tool for determining individual exposures.
Before deployment, materials that might interfere with future chemical analyses were reduced with various solvents. The researchers then developed a way to extract and analyze an unprecedented number of chemical compounds from the silicone wristbands after they are worn. To test the process, they provided 38 volunteers, eight of whom were roofers, with wristbands. After wearing them during day-to-day activities for 30 days, the volunteers placed their wristbands in a Teflon bag and sent them to the researchers for analyses. The scientists identified 49 different absorbed substances, including polycyclic aromatic hydrocarbons (PAHs), flame retardants, and compounds from pesticides and consumer products. They detected absorbed PAHs, including 12 on a federal priority list of harmful pollutants, in all of the roofers’ wristbands.
The test revealed that the wristbands are easy to use, that people will wear them, and that they had very good analytical sensitivity. The researchers say they can screen for, and quantify, over 1,000 chemicals that may accumulate in the wristbands, including PCBs, industrial chemicals, and consumer and pharmaceutical products.
Exposure to bisphenol A linked with early-onset prostate cancer
In an NIEHS-supported study, researchers found that men with prostate cancer had higher urinary levels of bisphenol A (BPA), suggesting that urinary BPA level is an independent prognostic marker of prostate cancer. Scientists also report new information about a possible mechanism for the BPA influence in transformation of prostate cells into cancer cells.
The researchers examined urine BPA levels in 60 urology patients and found that prostate cancer patients had higher levels of BPA, 5.74 micrograms per gram (95 percent confidence interval; 2.63, 12.51) than patients without prostate cancer, 1.43 micrograms/gram (95 percent confidence interval; 0.70, 2.88) (p = 0.012). The difference in BPA levels was even more significant in patients who were younger than 65.
They also examined how prostate cancer cells and normal prostate cells responded to low doses of BPA. For both types of cells, BPA exposure increased the percentage of cells with more than the normal number of centrosomes two-fold to eight-fold, and also induced other cellular changes. These findings suggest low-dose BPA may lead to the development of prostrate cancer, by disrupting centrosome duplication.
Citation: Tarapore P, Ying J, Ouyang B, Burke B, Bracken B, Ho SM. 2014. Exposure to bisphenol A correlates with early-onset prostate cancer and promotes centrosome amplification and anchorage-independent growth in vitro. PLoS One 9(3):e90332. Story
Possible new autoimmune disease treatment without side effects
NIEHS grantees have discovered a compound that may be a safer alternative for treating autoimmune diseases. The compound works differently than currently used drugs, and the researchers think that it will likely have fewer side effects.
In previous work, the researchers had discovered that the toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppressed the immune system by targeting the aryl hydrocarbon receptor (AhR) in T cells. The researchers used this knowledge to screen for compounds that activated AhR, without harming cells, identifying 10-chloro-7H-benzimidazo[2,1-a]benzo[de]Iso-quinolin-7-one (10-Cl-BBQ) as a candidate. Further analysis showed that 10-Cl-BBQ binds to AhR inside T cells and changes the cells into regulatory T cells, which suppress the immune response.
The researchers tested 10-Cl-BBQ in mice with graft-versus-host disease, a condition in which the immune system tries to eliminate foreign cells. Daily injections of 10-Cl-BBQ completely suppressed the disease. The compound was rapidly metabolized and excreted, and was not toxic at the dosage used, making it a potential candidate for drug development.
Citation: Punj S, Kopparapu P, Jang HS, Phillips JL, Pennington J, Rohlman D, O’Donnell E, Iversen PL, Kolluri SK, Kerkvliet NI. 2014. Benzimidazoisoquinolines: a new class of rapidly metabolized aryl hydrocarbon receptor (AhR) ligands that induce AhR-dependent Tregs and prevent murine graft-versus-host disease. PLoS One 9(2):e88726. Story
Methylation in the adult mammalian brain
Research, funded in part by NIEHS, reveals new information about an epigenetic mechanism that regulates gene expression in the mouse brain. This mechanism may contribute to the neurodevelopmental disorder Rett syndrome and other neurological disorders.
Epigenetic changes, such as DNA methylation, control gene expression without changing DNA code. Historically, scientists believed methyl groups could only attach to a cytosine followed by a guanine (CpG). But in recent years, methyl groups have been found on other sequences. In the new work, the researchers conducted systematic analyses of DNA methylation in the adult mouse brain with single-base resolution, and also mapped genomic distribution.
They found that adult mouse neurons have both non-CpG and CpG methylation. They observed non-CpG methylation in DNA regions lacking CpG methylation, meaning that it can likely control gene expression independently of CpG methylation. Additional experiments showed that non-CpG methylation occurs postnatally, is dynamic, and can repress gene expression. They also found that non-CpG methylation and CpG methylation are both read by the methyl-CpG binding protein 2 (MeCP2 enzyme), which is important because MeCP2 mutations lead to problems in neural development and neuronal functions, and are also linked to the neurodevelopmental disorder Rett syndrome.
Citation: Guo JU, Su Y, Shin JH, Shin J, Li H, Xie B, Zhong C, Hu S, Le T, Fan G, Zhu H, Chang Q, Gao Y, Ming GL, Song H. 2014. Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nat Neurosci 17(2):215-222.
(Nancy Lamontagne is a science writer with MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)