Research links carbon nanotubes to lung cancer risk

Two studies take different approaches; show similar results

MORGANTOWN, W.Va. – Two recent studies — both taking different scientific paths — have each linked a popular new manmade material with the development of cancerous cells.

The research projects were conducted by scientists at West Virginia University and the National Institute of Occupational Safety and Health (NIOSH).

Carbon nanotubes, first created about 20 years ago, are tiny, fibrous materials 50,000 times thinner than a human hair with walls a single molecule thick. They are strong and long-lasting. Their physical and chemical properties have excited researchers and engineers, who are working around the world to discover new applications in supercapacitors, batteries, the automotive and aerospace industries, electronics, pharmaceutics, bio-engineering, medical devices and biomedicine.

However, the rush to exploit this new material has created a concern among scientists that widespread manufacturing and distribution of nanotubes may expose both workers and consumers to unknown risks.

Both new studies, published in online journals, note the similarity of the nanotube structure to the naturally-occurring structure of asbestos fibers that have been implicated in health consequences for a large number of manufacturing and construction workers.

Lan Guo, Ph.D., of WVU’s Mary Babb Randolph Cancer Center, along with several other WVU and NIOSH researchers, found a relationship between introduction of carbon nanotubes into the lungs of lab mice and the production of gene biomarkers which are known to change dramatically when lung cancer develops. The genes showed changes similar to those in human patients with lung cancer

Yon Rojanasakul, Ph.D., of the WVU School of Pharmacy, and his colleagues exposed human lung cells to carbon nanotubes in a laboratory. The cells developed malignant transformations similar to the early signs of lung cancer. They then injected these cells into lab mice, which developed tumors. 

“Multi-walled carbon nanotubes (MWCNT) are similar in structure to asbestos, a known human carcinogen that causes lung cancer and mesothelioma,” Dr. Guo said. “In previous studies, our collaborators at NIOSH demonstrated that MWCNT exposure rapidly produces significant pulmonary inflammation, damage and fibrosis. Several studies have pointed to fibrosis as a precursor to lung cancer.”

Guo’s team analyzed a set of 63 lung cancer biomarker genes, most of which are known to change dramatically when lung cancer develops. Of the 63 genes analyzed, 14 changed dramatically at either seven days or 56 days following exposure and four of the 14 stayed abnormal during both time intervals.

“I want to be cautious about these findings,” Guo said. “So far there has been no direct evidence to declare that exposures to multi-walled carbon nanotubes induce or cause cancer. However, our study of lung disease development in an animal model indicates there are harmful effects to some genes known to be associated with lung cancer progression in humans.” She added that these results could be used for the medical surveillance of people who work in occupations in which they are exposed to multi-walled carbon nanotubes.

Dr. Rojanasakul’s research focused on a related material, single-walled carbon nanotubes (SWCNT). He and his research team, which also included NIOSH and Cancer Center researchers, first introduced the nanotubes into human lung epithelial cells which had been grown in laboratory cultures. Over 12 to 24 weeks of observation, the cells displayed many of the same changes observed in cancer cells.

“Carcinogenesis is a multistep process requiring long-term exposure to the carcinogens,” Rojanasakul said.  “We have developed a chronic exposure model in which human lung cells were continuously exposed to a low dose of SWCNT in culture over a prolonged time period.”

The transformed human cells were then injected into mice, which developed easily visible tumors at the injection sites. Control mice, which were injected with human lung cells that had not been exposed to carbon nanotubes, did not develop tumors.

The Guo study was published online May 23 in the journal “Toxicology and Applied Pharmacology.” Co-authors are Maricica Pacurari, Ph.D., Ying-Wooi Wan and Dajie Luo of the Mary Babb Randolph Cancer Center; and Yong Qian, Ph.D., Dale Porter, Ph.D., Michael Wolfarth, Min Ding, Ph.D., and Vincent Castranova, Ph.D., of NIOSH. To view the study online go to http://dx.doi.org/10.1016/j.taap.2011.05.012.

The Rojanasakul study was posted online in early June in “NANO Letters,” a publication of the American Chemical Society. Co-authors are Liying Wang, Ph.D., and Vincent Castranova, Ph.D., of NIOSH; Yongju Lu, Sudjit Luanpitpong, and Varisa Pongrakhananon, Ph.D., of the WVU School of Pharmacy; and William Tse, M.D., of the Mary Babb Randolph Cancer Center. To view the study online go to http://pubs.acs.org/doi/pdf/10.1021/nl2011214.