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Q&A: A Proteomic Approach to Investigating the Effects of Cell Phone Radiation


Name: Dariusz Leszczynski
Position: Research Professor: STUK – Radiation and Nuclear Safety Authority, Helsinki, Finland
Background: Guangbiao Professor, Bioelectromagnetics Laboratory, Zhejiang University School of Medicine, Hangzhou, China; Assistant Professor of Dermatology, Department of Dermatology, Harvard Medical School

With the World Health Organization's May decision to classify cell phone radiation as "possibly carcinogenic," the devices' potential health risks have been back in the news.

Dariusz Leszczynski, a research professor at STUK, Finland's Radiation and Nuclear Safety Authority, has been studying the effects of cell phone use on human cells for a decade, investigating changes in protein expression and activity in response to their radiation. Using broad proteomic screens, he and his colleagues have identified a number of proteins potentially affected by cell phone use, including heat shock protein 27 and MAP kinase.

Leszczynski also writes frequently about the topic on his blog, Between a Rock and a Hard Place. This week ProteoMonitor spoke with him about the potential for applying proteomics to the question of cell phone safety, the sometimes controversial nature of the work, and where he hopes to focus the research moving forward.

Below is an edited version of the interview.

What have you found using proteomics to investigate the effects of cell phone radiation?

I began in 2001 looking at the proteome of endothelial cells lines to investigate changes in response to mobile phone radiation. [In that first work] we found broad changes in protein expression and also a significant increase in protein phosphorylation, including in heat shock protein 27 and p38MAP kinase. Later we compared two different endothelial cell lines looking at some 800 proteins and found around 40 to 50 proteins [whose] expression was potentially affected.

Then we took this further, asking the question, 'Can we pick out [response to mobile phone radiation] in cells that are within the human body and responding to many, many different stimuli?' This we did in a pilot study where we took 10 people and exposed them for one hour to mobile phone radiation on a small area of skin on one arm. Then a surgeon took a biopsy of skin from this exposed area and another from another area that wasn't exposed as a control sample, so each person was their own control. We ran those samples on 2D gels and compared them, and when we looked at differences in protein expression between cells that were exposed and those that were not, we found changes in expression in all of these people.

Because of lack of funding and small sample size we weren't able to identify what the proteins were that responded to the mobile phone radiation, but we're hoping to get more funding for a larger study of around 50 people. To [get that funding], though, first we needed to demonstrate that we really can, using proteomics, find changes in protein expression [in response to mobile phone radiation]. So that's why we did this first pilot study.

Where else do you hope to take this research going forward?

What we would like to do in the future is more targeted analysis, using a protein chip for certain proteins or fractionating or enriching for certain types of proteins, for instance. In this way we could improve our chances of finding smaller changes [in protein expression], because you can't expect that this kind of very weak signal [from mobile phones] will cause a really dramatic change in protein expression.

You find in proteomic analyses that [often] proteins that are important for the regulation of functions of cells – different kinases, and so on – are expressed in very small amounts. And when we analyze them together in batch with other [more abundantly] expressed proteins, we find that we are losing possible [hits] because their changes are minute compared to [abundantly] expressed proteins. So we think it will be necessary to not examine the whole cell proteome but to fractionate and break it into smaller components and also maybe enrich for certain types of proteins. This way changes that look insignificant might become significant. It might not be a doubling or tripling of the expression of a protein — a 20 percent change might be enough to confirm that it is really significant. But if you're examining the whole proteome, this 20 percent change might vanish in your statistical analysis.

Any particular classes of proteins you'd like to target first?

There are. Everything depends on money, but one approach would be to look at the phosphoproteome and try to identify all phosphoproteins that one can find and see what kind of changes in phosphorylation there are in response to mobile phone exposure. So that's one thing – a more general approach to find all the pathways or processes that might be activated or inactivated because of changes in protein phosphorylation.

Another study that I would like to do – there have been three publications concerning effects of mobile phone radiation on stress protein pathways, on MAP kinase pathways. So we would like to do a really targeted approach looking at changes especially in phosphorylation but also in expression in those proteins that belong to MAP kinase signaling pathways, because it's known that activation of stress response pathways happens in cells that become carcinogenic. So this could be an indication of the possibility of the development of cancer.

You expect that changes in phosphorylation will be key to understanding the effects of cell phone radiation?

We saw an increase in phosphorylation of Hsp27 of between two-fold and six-fold after exposure to mobile phone radiation. So in the expression of proteins there might only be very small changes, but the changes in the activity of proteins might be the more important statistic. So what we would like to do is to examine not so much the expression of proteins but changes like phosphorylation, the changes in activity.

You mentioned difficulties getting funding for proteomic research into cell phone radiation. Is this due to a skepticism about proteomics in general, or is it more specific to this particular area of research?

Right now we are sort of at a crossroads because we don't have funding for more proteomics studies [into mobile phone radiation]. As it was explained to me by a scientist working in the [mobile phone] industry, if one does a proteomic screening, [one can] always find some proteins that will be affected, but it requires much further study to define whether this effect in the cell has enough power to affect the biology of the cell. And [the scientist] said that when you perform this type of study, when you publish this kind of proteomics study, then you will have stories in the newspapers scaring people saying that this protein is changing or that protein is changing.

It's important to remember that this sort of screening study is the beginning, after which it's necessary to confirm using other methods that these changes [in expression or activity] are really happening, and then find out whether those changes are significant enough to alter physiological processes in the cell.

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So you believe funding for such work is hard to come by because of the potential for controversy caused by overhyping results from preliminary proteomic screens?

There is an idea in this field – mobile phone radiation – that people don't want this type of information because it may affect the opinion of consumers. They like studies that look at a particular protein or a particular hypothesis — that is OK. But if you start screening [using proteomics], then you are a bad guy. People will say, 'No, this is not the way to do it, you have to have a hypothesis.' But what if I screen and find out what the changes are, and then when I know what proteins or processes are potentially affected I test it so that I can make a much more informed decision about my hypothesis?

Scientists should do experiments, and if those experiments find something then you publish a study. What the news media does with this study is an entirely different thing. There are some media outlets that report very responsibly. But of course some media outlets are looking for a catchy story. And in this way it may happen that some findings that come from [proteomic] screening, where we don't know exactly what the significance is, get out and are spoken about and some people are scared by it.

But if I start screening and [wait to publish until after] confirming the screen results and … the physiological relevance of the [differentially expressed] proteins, it will be maybe 10 years before I can publish that information. If, [instead], I find by screening a number of proteins that are affected, and I publish them, then when I publish I expect and hope that other scientists will say, 'OK, this is a protein that is interesting to me. I will look at this.' I release this information to the scientific community and the scientific community either validates my findings or they say that, 'No, this is a wrong finding, nothing is happening.'

Have topics you'd like to see covered in ProteoMonitor? Contact the editor at abonislawski [at] genomeweb [.] com.

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