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Detection of Carcinogen–Macromolecular Adducts in Humans

Building 37, Room 2CO5 National Cancer Institute Bethesda, MD 20892

D. K. Manchester

Building 37, Room 2CO5 National Cancer Institute Bethesda, MD 20892

A. Povey

Building 37, Room 2CO5 National Cancer Institute Bethesda, MD 20892

C. C. Harris

Building 37, Room 2CO5 National Cancer Institute Bethesda, MD 20892

A major concern of molecular epidemiology is the identification of individuals at increased risk of cancer by obtaining evidence of high exposure to carcinogens that may lead to pathobiological lesions in target cells. DNA is considered to be a target for modification by mutagens and carcinogens; therefore, damage to DNA can be used as an internal, molecular dosimeter of carcinogen exposure. The reactive species of these carcinogens may bind either directly to DNA to form adducts or indirectly to cause secondary DNA lesions through free radicals and aldehydes. Highly sensitive and specific methods have been developed to measure DNA lesions and DNA repair products that are found in biological specimens from humans exposed to carcinogens in the environment. For example, DNA adducts have been measured in cells and tissues from people exposed environmentally to carcinogenic polycyclic aromatic hydrocarbons or alkylating agents. Antibodies recognizing carcinogen-DNA adducts have also been detected in human sera. Carcinogen-protein adducts are also being used as molecular dosimeters of carcinogen exposure. The advantages and limitations of the various methods used to measure carcinogen-macromolecular adducts are discussed here. The use of two or more complementary assays to obtain confirmatory results is recommended.

International Journal of Toxicology, Vol. 8, No. 5, 913-932 (1989)
DOI: 10.3109/10915818909018052


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