Factors contributing to biomarker responses in exposed workers

''...[Th]e proper study of mankind is man'' (Pope, circa 1733/1734). Human monitoring fits this notion and monitoring after exposure to genotoxic agents is now an established discipline. It is possible in many situations to identify humans exposed to potentially toxic materials in the workplace and the environment. Responses are often measured in peripheral lymphocytes because these cells can be acquired by a generally socially and ethically acceptable, minimally invasive route. In the early 1960s, chromosome damage in these cells was one of the first endpoints to be used as a biomarker and benzene was one of the first chemicals investigated. Although a causal relationship between chromosome damage and cancer has not been proven, it has been suggested to have some prognostic significance for future cancer onset. With other genetic biomarkers this is as yet not the case, but there are now many biomarkers for different areas of toxicology. Other well-established genetic biomarkers include the detection of hprt mutations, micronuclei and sister chromatid exchanges. However, for interpretation of responses, the issue of confounding factors must be addressed. As in most human studies, there tends to be a high degree of interindividual variability in response to chemical insults. Some non-exposed control individuals exhibit as high a level of damage as some exposed individuals and some of these have levels of damage as low as many of the controls. Thus, it is only the mean values of the groups that can substantiate an exposure related-problem; the data on an individual basis are still of limited use. While human lymphocytes remain the most popular cell type for monitoring purposes, sperm, buccal, nasal, epithelial and placental cells are also used. Confounding factors affect responses in all cell types. There are endogenous confounding factors such as age, sex, genetic make-up and exogenous confounding factors including lifestyle habits such as smoking, drinking, etc. There are biomarkers of exposure, effect and susceptibility and the last may be influenced by the genotype and polymorphism genes existing in a population. From our own studies, confounding effects will be considered in relation to workers exposed to vinyl chloride and petroleum emissions. The relationship between the biomarkers and various factors which influence them is complex. Sometimes the variables are not completely independent of one another. (C) 1999 Elsevier Science B.V. All rights reserved.