Biomarkers: What are they and why do we study them?

In my previous post, I stated that as part of the research of which I was involved, we took blood and urine samples from our subjects, i.e. the guys we were studying. These men are exposed to chemicals during the normal course of their workday. [I say men because the all the people in our study were men. We would have happily used women in our study, but the industry we were studying is dominated by male workers, and we did not find any females to participate or who even worked at that type of job.] While the men were exposed to numerous chemicals, we were interested in one specific chemical that is known to cause detrimental health effects. While the subject was working with this chemical, we had a personal air sampling device clipped to his clothing in the shoulder area. This gave us estimate of the amount of chemical that was in his breathing air space. It was important for us to measure the breathing air space to determine exposure because the worker was spraying this chemical, so the chemical concentration would not be uniform in the air around him. As an example, if you are standing in your house, you can presume the air around you is evenly mixed. However, if while standing there, you spray air freshener or something like that, then as you spray and right after you spray, there will be a very high concentration of the air freshener in front of the direction you sprayed it. There will be a lower, but still high concentration right behind the sprayer, presumably this would be where you are, as the spray mixes. The high concentration will quickly spread out, and the freshener will mix in the rest of the room. If the house’s ventilation system is operating at the time, the freshener will mix faster than if the ventilation is currently off. Thus, the air sample that was taken in the breathing air space gave us an estimate of what the worker would have breathed in had he not been wearing a respirator. All the workers wore respirators though. Some wore half-face filter type respirators (similar to what you buy at a hardware store), which generally reduce the chemical concentration in the air breathed in by a factor about ten or so, if they are worn properly. Some workers wore supplied-air respirators, like a firefighter only these were attached to a hose with an outside air supply. This type of respirators generally reduces the chemical concentration in air breathed in by a factor of 1000. Therefore, we got an estimate of what the worker was exposed to in the air but not of the amount that made it into the lungs.

After the subject worked with the chemical, we applied and quickly removed tape strips (medical tape) to his arms, wrists, hands, and neck to determine the amount of the chemical that made it onto his skin in those areas. The medical tape removed the very top layer of epidermis and any chemical that was in that layer. Basically it was like we applied and then removed a band-aid without the gauze section. Thus, the tape strip gave us an estimate of how much chemical made it on to his skin, but it couldn’t tell us how much of the chemical actually made it through the layers of the skin and into the blood stream. Previous research had indicated that it was possible for this chemical to be absorbed through the skin. Despite what some people might think, skin is not impervious to chemicals. If it was, the nicotine patch and the estrogen patch wouldn’t work.

To summarize, we could estimate what the worker was exposed to via inhalation and dermal exposure, but we didn’t know what he actually absorbed or what made it into his body. That is where biomarkers can be useful. Biomarkers are measurements of a chemical or some other tell-tale sign of exposure in some biological sample. They can be measured in the blood, urine, fecal matter, exhaled breath, and many other bodily fluids or materials. Some materials are used more frequently because they are a lot easier to get. It is much easier to get someone to agree to urinate in a cup then to let you do a spinal tap for spinal fluid. Which bodily material is used also depends on what the chemical of interest is. If you are looking for a volatile chemical, the exhaled breath might be used. To get the exhaled breath, the person simply exhales into a specially designed glass tube. Similarly, a suspected drunk driver who has just been pulled over by the police, may be asked to breath into a breathalyzer. The concentration of the alcohol, or chemical, in that air can then be measured. This is a biomarker. If the chemical or its metabolite is excreted quickly, then it would be more useful to study the urine than the blood because there would probably be higher concentrations in the urine than the blood. However, the concentration in the urine is generally more representative of short term exposure, while the blood is more representative of long-term exposure.

The metabolism of the chemical is very important because it indicates what chemical you are actually looking for in the body and also where to look for it. For example, when a person is exposed to lead, it does not change into another chemical because lead is an element. Thus, blood lead level is a biomarker used to indicate exposure to lead. A person’s intoxication level can be measured by exhaled breath as stated. A suspected intoxicated person can also have a blood sample withdrawn, and the amount of alcohol in the blood can be measured. It is called the blood alcohol content, and it a biomarker of alcohol exposure. The body metabolizes alcohol and uses it for fuel, so looking for it in the urine is not all that useful, or least not for the police. Alcohol in the urine is more indicative of consumption hours beforehand (i.e. it doesn’t tell the police how drunk the person is at that moment, crucial for legal reasons), and it is not completely accurate because the rate and amount that a person metabolizes alcohol differs from another person. Like alcohol, many other chemicals that people are exposed to, are metabolized or partially metabolized by the body. Unlike alcohol, if it is a chemical that the body does not need and can’t use for nutrition, then the body will generally try to get rid of it as quickly as possible, if it can. The chemical we were studying in our research was like this. The body has no use for it, so it is partially metabolized and excreted. Thus we looked for the metabolite, not the chemical itself, in the urine or blood. To what degree a chemical or metabolite can be found in the urine versus the blood versus some other bodily fluid or tissue depends on the physical and chemical properties of the chemical or its metabolite. The metabolism, storage, and excretion pathway in the body of different chemicals is the subject of fascinating research and possibly another blog post.