Biomarkers are broadly defined as indicators signaling events in biological systems or samples. They have been classified as markers of exposure, markers of effect, and markers of susceptibility.
Biomarkers Used to Identify or Quantify Exposure to Radon
Biomarkers of exposure to radon and its progeny include the presence of radon progeny in several human tissues and fluids, including:
Although the presence of radon progeny in these tissues and fluids indicate exposure to radon, exposure to uranium or radium may also result in the presence of these decay products.
Biomarkers of radon or radon progeny exposure may be present after any exposure duration (acute, intermediate, and chronic). Because of the relatively short half-lives of most radon progeny, with respect to a human lifetime, the time at which the biological sample is taken relevant to time of exposure may be important. However, for the longer lived progeny the time factor is less critical.
Models are available that estimate exposure to radon from the levels of stable radon daughter products, lead-210 and polonium-210, that are detected in teeth, bone, and blood. In vivo gamma spectrometric measurements of lead-210 in skull bones have been made in miners exposed to very high radon levels. Lead-210 is incorporated in bone and has a biological half-life of 10-15 years. Its physical half-life is 22.2 years. Owing to the insensitivity of the method and the influence of other sources of lead-210 intake (water, food, etc.) such measurements have not been feasible for persons exposed to radon in dwellings. These models also make several assumptions, and uncertainties inherent in all models are involved in these estimates. Therefore, presently, these estimated levels of biomarkers of exposure are not significantly useful for quantifying exposure to radon and radon progeny. Quantification of exposure to radon is further complicated by the fact that radon is a ubiquitous substance and background levels of radon and radon progeny are needed to quantify higher than average exposures.
Exposure to ionizing radiation increases the number of chromosome aberrations in human blood lymphocytes. This increase mainly reflects the last year of exposure, owing to repair mechanisms, and limits the usefulness of this parameter as a marker of long-term exposure.
Biomarkers Used to Characterize Effects Caused by Radon
Determining the health effects of exposure to low levels of radiation has been much more difficult than determining the effects of high-level exposure, for two reasons.
- Cells can repair some damage caused by low levels of radiation absorbed over long periods of time.
- It is difficult to tell whether a particular cancer was caused by radiation, by one of the more than 300 other known carcinogens in the environment, or by other unknown factors.
As previously mentioned, the primary organ identified in both human and animal studies following exposure to radon and progeny is the lung. Alterations in sputum cytology have been evaluated as an early indicator of radiation damage to lung tissue. The frequency of abnormalities in sputum cytology, which may indicate potential lung cancer development, increased with increasing cumulative exposures to radon and radon daughters. Although abnormal sputum cytology may be observed following radon exposure, this effect is also seen following exposure to other xenobiotics, including cigarette smoke. In addition, even though increases in the frequency of abnormal sputum cytology can be measured, they may not provide a reliable correlation between levels in human tissues or fluids with health effects in exposed individuals.
A dose-response relationship between chromosome aberrations and increased environmental levels of radon has been reported. Although the presence of chromosomal aberrations is a biomarker of effect, the potential range of chemicals which could cause this effect is so great that it would not necessarily be considered radon-specific.
In studying lung cancers, researchers have associated specific mutations in the p53 tumor suppresser gene with radon exposure as well as cigarette smoke exposure. Recently, dose-response curves have been established to link the effects of smoking and radon exposure to the extent of p53 mutations. Use of p53 mutations as a biomarker for exposure has been proposed and examined by Yngveson. In a normal lung cancer tumor, mutations on the tumor suppresser gene occur between exons 5 and 8, with a common pattern of conversions of guanines and cytosines to thyamines and adenosines, respectively. In a radon exposed cell with p53 mutations, alterations are seen to occur only on exons 5 or 6 and usually only on codon 249 where guanines are subsequently converted to thyamines (AGG --> ATG). However, the percentage of times out of the total transversion rate is not very high (<60%). Radons effects on p53 need to be studied more thoroughly in order to better determine whether specific mutations can be used as biomarkers for radon exposure linked cancers. For more details see the section on molecular and genetics effects from radon.