DNA adducts as markers of exposure and risk.
Many carcinogens exert their biological effects through the formation of DNA adducts by metabolically activated intermediates. Detecting the presence of DNA adducts in human tissues is, therefore, a tool for molecular epidemiological studies of cancer. A large body of evidence demonstrates that DNA adducts are useful markers of carcinogen exposure, providing an integrated measurement of carcinogen intake, metabolic activation, and delivery to the target macromolecule in target tissues. Monitoring accessible surrogate tissues, such as white blood cells, also provides a means of investigating occupational or environmental exposure in healthy individuals. Such exposure to carcinogens, e.g. to polycyclic aromatic hydrocarbons, has been demonstrated in several industries and in defined populations, respectively, by the detection of higher levels of adducts. Adducts detected in many tissues of smokers are at levels significantly higher than in non-smokers, although the magnitude of the elevation does not predict the magnitude of the risk. While such associations do not demonstrate causality, they do, importantly, lend plausibility to observed associations between smoking and cancer. However, there is still resistance to the notion that such monitoring can inform, rather than merely confirm, epidemiological investigations of cancer causation. Interestingly, smoking was recently causally linked to cervical cancer after years of being considered a confounding factor; yet smoking-related adducts have been known to be present in cervical epithelium for some time. In the few prospective studies thus far, elevated adduct levels have been found in individuals who subsequently developed cancer compared with individuals who did not. The potential for biomarker measurements, such as DNA adducts, to provide answers to the origin of many cases of human cancer for which an environmental cause is suspected, needs to be exploited more fully in future epidemiological studies.
Phillips
David H
DH
Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton, UK. david.phillips@icr.ac.uk
D002273:Carcinogens / Q000633:toxicity*; D018736:DNA Adducts; D004784:Environmental Monitoring; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics; D018570:Risk Assessment; D012907:Smoking / Q000009:adverse effects; D014026:Nicotiana
D002273:Carcinogens; D018736:DNA Adducts