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). 2-acetylaminofluorene (AAF) and cisplatin by quantitative immunoassays, immunohistochemistry, atomic absorbance spectrometry (AAS) and (32)P-postlabeling. A study measuring PAH-DNA adducts in blood cell DNA of subjects ingesting charcoal-broiled meat showed a transient increase in PAH-DNA adducts measured by enzyme-linked immunosorbent assay (ELISA) during the ingestion period. In studies designed to investigate adduct processing during chronic administration of a chemical carcinogen, a dose-response relationship has been established between liver DNA adducts and the level of 4-aminobiphenyl (ABP) given chronically to male and female mice. Immunoaffinity chromatography has been used to separate DNA adducts of ABP in human DNA and these have been quantified by 32P-postlabeling. DNA adducts have been localized immunohistochemically in preneoplastic liver cells (identified by other markers) of rats fed AAF, in halos prepared from livers of rats fed AAF, and in embryos of rats exposed to N-AC-AAF in culture. DNA adducts of AAF have been identified in exposed CHO cells by electron microscopy. The extent of cisplatin-DNA adduct formation in nucleated blood cell DNA of cancer patients has been positively correlated with disease response in breast, colon and ovarian cancer patients receiving platinum drug-based chemotherapy. In animal models cisplatin-DNA adducts have been shown to form in high concentrations in mitochondria.