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, immunoaffinity chromatography (IAC), atomic absorbance spectrometry (AAS) and P-32-postlabeling. Studies are being conducted to measure PAH-DNA adducts in blood cell DNA of coke oven workers, aluminum plant workers, 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). Aromatic amine-DNA adducts are being concentrated from human lung DNA by IAC and quantified by P-32-postlabeling. The extent of cisplatin-DNA adduct formation in nucleated blood cell DNA of cancer patients (measured by cisplatin-DNA ELISA) has been positively correlated with disease response in ovarian cancer patients receiving platinum chemotherapy. This association is being further investigated in blood samples from previously-untreated ovarian cancer patients, all given the same protocol. Platinum-DNA adducts have been measured in placenta and blood cell DNA from a woman given cisplatin and carboplatin for ovarian cancer during pregnancy. This human exposure was modeled in the patas monkey, and adducts were measurable in both maternal and fetal tissues. Blood cell platinum-DNA adducts have been correlated with dose by both ELISA and AAS in samples from testicular cancer patients during 3 cycles of platinum-drug chemotherapy. An antiserum specific for the anti-AIDS drug, 3'-azido-2',3'-dideoxy-thymidine (AZT), has been used to establish an RIA and immunohistochemical localization for AZT incorporated into the DNA of human HL 60, hamster Chinese hamster ovary (CHO) and mouse NIH 3T3 cell lines. Incorporation of AZT into DNA by radiolabeling correlated well with that determined by RIA. The highest concentrations of AZT incorporated into CHO cell chromosomal DNA colocalized with regions of DNA in Z conformation.