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Abstract

¹Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland
²Department of Community Medicine, Mount Sinai School of Medicine, New York, New York

Abstract

Human DNA adduct formation (covalent modifcation of DNA with chemical carcinogens) is a promising biomarker for elucidating the molecular epidemiology of cancer. Classes of compounds for which human DNA adducts have been observed include polycyclic aromatic hydrocarbons (PAHs) , nitrosamines, mycotoxins, aromatic amines, heterocyclic amines, ultraviolet light, and alkylating cancer chemotherapeutic agents. Most human DNA adduct exposure monitoring has been performed with either ³²P-postlabeling or immunoassays, neither of which is able to chemically characterize specifc DNA adducts. Recently developed combinations of methods with chemical and physical end points have allowed identifcation of specifc adducts in human tissues. Studies are presented that demonstrate that high ambient levels of benzo[a]pyrene are associated with high levels of DNA adducts in human blood cell DNA and that the same DNA adduct levels drop when the ambient PAH levels decrease signifcantly. DNA adduct dosimetry, which has been achieved with some dietary carcinogens and cancer chemotherapeutic agents, is described, as well as studies correlating DNA adducts with other biomarkers. It is likely that some toxic, noncarcinogenic compounds may have genotoxic effects, including oxidative damage, and that adverse health outcomes other than cancer may be correlated with DNA adduct formation. The studies presented here may serve as useful prototypes for exploration of other toxicological end points. -- Environ Health Perspect 104(Suppl 5) :883-893 (1996)

Key words: polycyclic aromatic hydrocarbons, occupational exposure, ambient benzo[a]pyrene, enzyme-linked immunosorbent assay, ³²P-postlabeling, fuorescence spectroscopy, gas chromatography-mass spectrometry, biomarkers