DNA adducts and related biomarkers in assessing the risk of complex mixtures.
Perera-FP; Schulte-P; Santella-RM; Brenner-D
Genetic toxicology of complex mixtures. Waters MD, Daniel FB, Lewtas J, Moor MM, Nesnow S, eds. New York: Plenum Press, Environmental Science Research, 1990 Jan; 39:271-290
This chapter critically evaluated the role of biological markers and molecular epidemiology in the risk management of environmental carcinogens, particularly of complex mixtures. The findings of recent studies which assessed macromolecular adducts formed by carcinogens were used to illustrate the potential and current limitations of this approach. The conceptual framework of biological markers was also reviewed, discussing specifically markers of internal dose, markers of biologically effective dose, markers of early biological effect, and markers of susceptibility. The advantages and disadvantages of biomarkers were discussed, including the facts that biomarkers can permit greater resolution in environmental research, can improve exposure assessment, can provide timely identification of individuals or groups at elevated risk of disease, have the potential to improve risk extrapolation between species and populations, offer improved understanding of the mechanisms of disease causation and progression, and improve epidemiological study design and inference. The disadvantages and limitations of biomarkers were that most lack adequate validation, and that the molecular epidemiological studies are complex and resource intensive. An overview was included of recent studies involving complex mixtures. The authors conclude that these early studies are encouraging in that macromolecular adducts and related biomarkers can ultimately be useful in identifying the operational carcinogenic constituents of complex mixtures and in estimating whether their effect is additive or interreactive. These can provide valuable insights into the nature and magnitude of interindividual variability and the need to factor this into quantitative risk assessment. The authors encourage the use of well designed molecular epidemiological studies in human populations with model exposures to single agents and to complex mixtures in order to gain the most from the use of these markers.
NIOSH-Author; Biological-monitoring; Bioassays; Carcinogenesis; Risk-analysis; Laboratory-animals; DNA-adducts; Molecular-biology
Waters-MD; Daniel-FB; Lewtas-J; Moor-MM; Nesnow-S
Genetic toxicology of complex mixtures