Immunologic methods for the detection of carcinogen adducts in humans.
Monoclonal antibodies have been developed which recognize a number of carcinogen-DNA and protein adducts. These antibodies can be used in highly sensitive competitive enzyme linked immunosorbent assays (ELISA) to detect femtomole levels of adducts in human samples. With the most sensitive antibodies, DNA adducts in the range of 1/10(8) nucleotides can be measured. In addition, antibodies to DNA adducts can be used to investigate immunohistochemically the localization of adducts in specific cell and tissue types. Antibodies recognizing benzo(a)pyrene diol epoxide-DNA have been used to monitor adducts in white blood cell DNA of foundry workers and placental and white blood cell DNA of smokers and nonsmokers. Because of antibody crossreactivity with structurally related adducts of other polycyclic aromatic hydrocarbons, this assay is not specific for benzo(a)pyrene adducts. Antibodies to the stable guanine imidazole ring opened aflatoxin-B1-DNA adduct have been used to detect elevated levels of adducts in liver tissue from Taiwanese hepatocellular cancer patients. Monoclonal antibodies against 8-methoxypsoralen-DNA have been used to monitor adducts in psoriasis and cancer patients treated with psoralen plus UVA light. These patients have also served as model systems for the development of immunofluorescence methods for adduct detection. Immunohistochemical staining of skin biopsies from psoriasis patients demonstrated specific staining of epidermal cells. With further increases in sensitivity, this method should be applicable to the detection of adducts in other human tissues. Adduct detection in humans is now established as a viable method for determination of exposure to certain chemical carcinogens. However, the relationship of adduct measurements to individual risk requires further investigation.
Santella
R M
RM
Division of Environmental Science, School of Public Health, Columbia University, New York, NY 10032.
Yang
X Y
XY
Hsieh
L L
LL
Young
T L
TL
D000348:Aflatoxins / Q000032:analysis / Q000276:immunology; D000911:Antibodies, Monoclonal; D002273:Carcinogens / Q000032:analysis*; D004247:DNA / Q000032:analysis* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D008730:Methoxsalen / Q000032:analysis; D011083:Polycyclic Compounds / Q000032:analysis / Q000276:immunology
D000348:Aflatoxins; D000911:Antibodies, Monoclonal; D002273:Carcinogens; D011083:Polycyclic Compounds; D004247:DNA; D008730:Methoxsalen