Ozone imperils skin: Exposure increases risk of carcinoma, study notes

August 1, 2009

Human skin cells exposed to the ozone in smog exhibit changes in signaling pathways that put them at increased risk for developing cancer.

Key Points

"There are many pollutants in the environment that are capable of damaging skin; the most well-characterized one is ultraviolet radiation," says senior investigator Hasan Mukhtar, Ph.D., Helfaer Professor of Cancer Research, department of dermatology, University of Wiconsin-Madison.

"In this study, we discovered that the ozone component of smog could be a major contributor by enhancing the activity of the enzymes and the receptors that play a critical role in conversion of inactive molecules to more toxic agents, thereby increasing the risk of environmental skin cancer," he says.

Part of the study focused on the cytochrome P450 system, "whose principal function is to convert whatever goes into the body to more water soluble molecules that are more easily excreted."

It is particularly important in the liver for the metabolism of many drugs and the clearance of toxins, but the process also takes place at the cellular level in the skin.

Metabolic activation of procarcinogens into reactive carcinogenic metabolites with the ability to bind cellular DNA in skin cells has been reported for this enzyme system.

The researchers exposed normal human epidermal keratinocytes for 20 minutes in an enclosed chamber to a "dose" of ozone (0.3 parts per million) that was well within the range typically found in urban environments (0.2 to 1.2 ppm). They looked at the effect on cell signaling pathways at three time points: immediately after, three hours after and six hours after that exposure.

There was a marked increase in the protein expression of isozymes CYP1A1, CYP1A2 and CYP1B1. Expressions of the first and third isozymes were more pronounced at three hours, while expression of the second was more pronounced at six hours.

Additional work determined that exposure to ozone decreased cytosolic levels of the aryl hydrocarbon receptor (AhR) protein - a ligand-dependent receptor that binds a variety of known environmental toxins and mediates their effects - and increased AhR translocation to the nucleus. It resulted in increased mRNA expression of AhR.

AhR also affects the epidermal growth factor (EGF) signaling pathway through "cross-talk" with the EGF receptor.

Dose response

Dr. Mukhtar says preliminary work suggests that there is a dose response to the concentration and duration of exposure to ozone, but the exact patterns of those responses are not yet clear. And while the effect is not permanent, it, likewise, is premature to say anything about how long it takes cells to recover from the ozone insult.

He cautions that while skin cultures are a good approximation of what likely occurs in vivo, unless studies on human subjects by controlled exposure to ozone are conducted, the repercussions of these findings for human skin health are not certain. Thus, the present studies should be validated in clinical studies.

Dr. Mukhtar says the most immediate implications of these findings are their potential for aiding the development of prevention interventions for environmental insults that cause skin aging and skin cancer.

Researchers would like to further understand the clinical implications of these findings for skin aging, he says.

"Is there any agent that we can supplement in a skincare product to ameliorate the effect so that people exposed to smog are protected?" he asks. He says he can envision a product similar to a sunscreen that protects against the harmful effects of UVB exposure.

Ozone exposure affects antioxidant levels and oxidative markers, and these findings also may have possible application in the anti-aging field. Investigators who conducted this study would like to pursue these lines of research.

Disclosure: This study was supported by the Estée Lauder Research Laboratories.