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), cisplatin and 3'-azido-2',3'-dideoxythymidine (AZT) by quantitative immunoassays, immunohistochemistry, immunoaffinity chromatography (IAC) and atomic absorbance spectrometry (AAS). Studies are being conducted to measure PAH-DNA adducts in blood cell DNA of subjects ingesting charbroiled beef and Army personnel exposed to oil well fires in Kuwait, using the benzo[a]pyrene-DNA enzyme-linked immunosorbent assay (ELISA) and the 6-fold more sensitive dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA). A previously-observed correlation between high levels of cisplatin-DNA adduct formation in nucleated blood cell DNA of cancer patients and favorable clinical responses is being investigated in blood samples from previously-untreated ovarian cancer patients, all given the same protocol. Modeling cisplatin exposure of an ovarian cancer patient during pregnancy, cisplatin-DNA adducts were measurable in both maternal and fetal tissues of five patas monkey dams exposed during gestation. Cisplatin-DNA adduct formation was shown to be 3- to 4-fold higher in mitochondrial DNA of Chinese hamster ovary cells as compared to genomic DNA. Increased cisplatin-DNA adduct formation in human breast tumor cells has been shown to be associated with an increase in signal transduction pathways that also enhances cisplatin cytotoxicity. The anti-AIDS drug, AZT, has been shown to bind DNA of mouse vaginal tissue (a target for tumorigenesis) and to induce bone marrow chromosomal aberrations in a dose-related fashion in animals given AZT in the drinking water for 28 days. Antisera being elicited against a benzene-protein adduct will be employed by DELFIA to establish an assay to be used for the monitoring of benzene-exposed workers in China and in the United States.