[DNA adducts as biological markers for human exposure to polycyclic aromatic compounds].
Polycyclic Aromatic Hydrocarbons (PAH) in human carcinogenesis is undisputed. Measurements of PAH-DNA adduct levels in easily accessible white blood cells therefore represent useful early endpoints in exposure intervention or preventive study. The successful applicability of DNA adducts as early endpoints depends on several criteria: (1) Adduct levels in easily accessible surrogate tissues should reflect adduct levels in target tissues (2) Toxic-kinetics and the temporal relevance should be properly defined (3) Sources of inter and intra individual variability must be know and controllable (4) Adduct analysis must have advantages as compared to other markers of PAH exposure. Higher proportions of subjects with detectable DNA adduct levels were found in exposed individuals as compared with non-exposed subjects, but saturation may occur at high exposure. Furthermore, DNA adducts levels varied according to changes in exposure. Intra-individual variation during continuous exposure was low over a short period of time (weeks), but varied significantly when longer time periods (months) were investigated. Intra-individual variation is currently only partly explained by genetic polymorphisms in genes involved in PAH metabolism. DNA adducts measurements have three advantages over traditional exposure assessment: (1) they can smooth the extreme variability in exposure which is typical for environmental toxicants and may integrate exposure over longer periods of time (2) Biological monitoring of DNA adducts accounts for all exposure routes (3) DNA adduct may account for inter-individual differences in uptake, elimination, distribution, metabolism and repair amongst exposed individuals. There is a sufficiently large scientific basis to justify the application of DNA adduct measurements as biomarkers in exposure assessment. However, their use in risk assessment requires further investigation.
Ken-Dror
Gie
G
Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine, Tel Aviv University. giekd@netvision.net.il
D001692:Biological Transport; D018736:DNA Adducts / Q000032:analysis* / Q000493:pharmacokinetics; D004781:Environmental Exposure; D004784:Environmental Monitoring / Q000379:methods*; D006801:Humans; D011084:Polycyclic Aromatic Hydrocarbons / Q000493:pharmacokinetics / Q000633:toxicity*
D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons