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Extramural Papers of the Month

By Jerry Phelps
November 2009

Carbon Nanotubes Can Affect the Lining of the Lungs

Carbon nanotubes are being used in many products including sports equipment, clothing and cosmetics and are being considered for additional uses such as targeted drug delivery devices. The toxicity of these materials is to a great extent unknown. However, a new collaborative study shows that inhalation of these particles can affect the outer lining of the lung. Long-term effects of the exposure are yet to be determined.

Laboratory mice were exposed, through inhalation, to nanotubules for a single six-hour window. Within one day, the research team noticed immune cells clustering on the surface of the pleura, the tissue that covers the outside of the lungs. Scarring or fibrosis began on the pleura about two weeks after exposure. These same effects at the same location are seen after exposure to asbestos, a known carcinogen.

The study showed that the scarring and immune responses disappeared about three months after the exposure. It is unknown if the effects would continue with chronic exposure to the nanotubes as is generally the case in asbestosis. Additional research with longer exposures is needed to determine the long-term effects of nanotube exposure.

Citation: Ryman-Rasmussen JP, Cesta MF, Brody AR, Shipley-Phillips JK, Everitt JI, Tewksbury EW, et al. ( NIEHS 2009. Inhaled carbon nanotubes reach the subpleural tissue in mice. Nature Nanotechology, DOI: 10.1038/nnano.2009.305

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Electronic "Nose" Smells Toxins

A modern-day sophisticated version of the canary in the coal mine has been developed by NIEHS grantees at the University of Illinois. As part of the NIH Genes, Environment and Health Initiative, the university researchers teamed up with a small biotechnology firm and developed a postage-sized sensor that detects poisonous gases and changes color to demonstrate the detection.

When the sensor is fully developed, it will be useful for detecting exposures to toxic materials in industrial and laboratory settings. While nuclear power workers, medical personnel and other people working with radiation wear badges to monitor their exposure, such technology does not exist as yet for chemicals. The investigators hope to be able to market the device within two years. And since the device monitors a variety of toxins, it can be customized for specific industrial settings. The sensor is engineered in such a way that the level of exposure can also be determined.

The developmental sensor detects 19 representative toxic industrial chemicals, including ammonia, chlorine, nitric acid and sulfur dioxide. In testing, the sensors were exposed to the chemicals for two minutes. Most of the chemicals were identified by the array color change in a matter of seconds and almost all were detected within two minutes.

Citation: Lim SH, Feng L, Kemling JW, Musto CH, Suslick KS. ( NIEHS 2009. An optoelectronic nose for the detection of toxic gases. Nature Chemistry 1:562-567.

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Arsenic and Heart Arrhythmia

The consumption of arsenic-contaminated drinking water is a known risk factor for skin and bladder cancer and is associated with other diseases including diabetes and cardiovascular diseases. Now, NIEHS-funded researchers report that low-level exposure to arsenic is associated with a prolongation of the Q-T portion of the heart rhythm.

Long Q-T syndrome (LQTS) is a disorder of the heart's conduction system that can be congenital or occur as a side effect of some medicines. The disorder affects the recharging of the heart after each heartbeat. LQTS can lead to an abnormal heart rhythm, fainting or even sudden death.

The researchers performed a cross-sectional analysis of elderly men from the Normative Aging Study. The study included 226 participants and analyzed toe nail clippings for arsenic content, which is a recognized biomarker for arsenic ingestion. Electrocardiograms were conducted on all study participants. Most of the participants lived in the Boston region and obtained their water from the Massachusetts Water Resources Authority. The arsenic concentration of this water resource is generally less than 1 microgram per liter, far below the current EPA standard of 10 micrograms per liter.

In the current study, there was no evidence of an effect of medication use on Q-T interval. The results of this study provide new information to guide efforts to reduce the arrhythmic effects of arsenic exposure.

Citation: Mordukhovich I, Wright RO, Amarasiriwardena C, Baja E, Baccarelli A, Suh H, et al. ( NIEHS 2009. Association between low-level environmental arsenic exposure and QT interval duration in a general population study. Am J Epdemiol 170(6):739-746.

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Prostate Gene Polymorphism Linked to Bladder Cancer

A fifty-member international and interdisciplinary team of researchers report the discovery of a single nucleotide polymorphism in the prostate stem cell antigen gene (PSCA) as a urinary bladder cancer gene. The research team includes NIEHS grantees from the M.D. Anderson Cancer Center and Dartmouth University.

The group conducted a genome-wide association study on 969 bladder cancer cases from Texas. This study was combined with ongoing efforts in three other US populations and nine European groups. A consistent association of a missense variant in the PSCA gene dubbed rs2294008 was found with bladder cancer in all populations. In combining all study subjects, the number of participants included 6,667 cases of bladder cancer and 35,590 controls and produced a highly statistically significant result.

The missense variant alters the start codon, is thought to shorten the protein by nine amino acids, and reduces promoter activity. Resequencing the PSCA genomic region identified rs2294008 as the only common missense polymorphism in the gene. Recent studies demonstrated that the same alteration is associated with gastric cancer in an Asian population. Whether this is true for people of European descent remains to be seen. Additional studies are planned to determine the physiological significance and functional consequences of the variant gene.

Citation: Wu X, Ye Y, Kiemeney LA, Sulem P, Rafnar T, Matullo G, et al. ( NIEHS 2009. Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer. Nat Genet 41(9):991-995.

(Jerry Phelps is a program analyst in the NIEHS Division of Extramural Research and Training. Each month, he contributes summaries of extramural papers to the Environmental Factor.)

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