USE OF IMMUNOLOGICAL TECHNIQUES TO STUDY THE INTERACTION OF CARCINOGENS WITH DNA

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Antibodies specific for carcinogen-DNA adducts have been used to quantify DNA modification in biological samples substituted with polycyclic aromatic hydrocarbons (PAH), aromatic amines and cisplatin by quantitative immunoassays, immunohistochemistry, atomic absorbance spectrometry (AAS) and (32)P-postlabeling . Studies are being conducted to measure PAH-DNA adducts in blood cell DNA of coke oven workers, aluminum plant workers and subjects ingesting charbroiled beef using a benzo[a]pyrene-DNA enzyme-linked immunosorbent assay (ELISA). The sensitivity of this assay has recently been improved 4- to 5-fold through the use of the DELFIA system with a Europium (fluorescent) end-point. Processing of aromatic amine-DNA adducts during chronic administration of either 2-acetylaminofluorene (AAF) or 4-aminobiphenyl (4-ABP) has been shown to be compound-, tissue- and sex-specific, and to have variable relationships with tumorigenesis in the same organs. A 370 base pair fragment is being used to study the effects of nucleotide composition on the localization of AAF-DNA adduct formation in livers of rats chronically-fed AAF. DNA adducts of ABP are being purified from human DNA by immunoaffinity chromatography and quantified by (32)P-postlabeling. The extent of cisplatin-DNA adduct formation in nucleated blood DNA of cancer patients (measured by cisplatin-DNA ELISA) has been positively correlated with disease response in breast, colon and ovarian cancer patients receiving platinum drug-based chemotherapy. The association with disease response did not hold for platinum-DNA adducts measured by AAS and was not statistically-significant for protocols (colon and breast) which showed poor overall response rates. Platinum-DNA adducts have been measured in tissues of a woman treated with platinum drugs for ovarian cancer during pregnancy. An antiserum specific for the anti-AIDS drug, 3'-azido-2',3'-dideoxythymidine (AZT) has been studied for cytotoxicity and DNA incorporation in human HL 60, hamster CHO and mouse NIH 3T3 cell lines. Incorporation of AZT into DNA has been demonstrated by radiolabeling and immunohistochemistry.