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Semiquantitation of Polycyclic Aromatic Hydrocarbon-DNA Adducts in Human Esophagus by Immunohistochemistry and the Automated Cellular Imaging System

Laboratory of Cellular Carcinogenesis and Tumor Promotion [H. E. v. G., R. L. D., O. A. O., M. C. P.], Laboratory of Pathology [J. A. S., D. E. K.], Cancer Prevention Studies Branch, Center for Cancer Research [M. J. R., S. M. D., P. R. T.], and Biometric Research Branch [G-Q. W., P. S. A.], Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, Maryland 20892, and Cancer Institute, Chinese Academy of Medical Sciences, Beijing, China 100021 [Y-L. Q., Z-W. D.]

It has been suggested that ingestion of polycyclic aromatic hydrocarbons (PAHs) may contribute to the high incidence and mortality of esophageal cancer in Linxian, China. To explore this relationship a semiquantitative immunohistochemical staining method was developed for localization of PAH-DNA adducts. Nuclear color intensity (bright field average pink intensity per nucleus for >1000 cells) was measured using the ChromaVision Automated Cellular Imaging System (ACIS). Paraffin-embedded sections of cultured human keratinocytes exposed to increasing concentrations of 7ß,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE) were incubated with BPDE-DNA antiserum and served as an internal positive control (standard curve). Values for nuclear staining intensity correlated directly with BPDE exposure concentration (r² = 0.99) and were reproducible. DNA adduct levels determined by BPDE-DNA chemiluminescence immunoassay in DNA from BPDE-exposed keratinocytes, correlated with BPDE exposure concentrations (r² = 0.99), showing that nuclear staining intensity determined by ACIS correlated directly with BPDE-DNA adduct levels determined by chemiluminescence immunoassay. The ACIS methodology was applied to 5 human samples from Linxian, and significantly positive nuclear PAH-DNA adduct staining was observed in this group when compared with esophageal tissue from 4 laboratory-housed monkey controls and 6 samples obtained at autopsy from smokers and nonsmokers in the United States. Nuclear PAH-DNA staining was absent from Linxian samples when serial sections were incubated with normal rabbit serum (negative control) and was significantly reduced on incubation with BPDE-DNA antiserum absorbed previously with the immunogen BPDE-DNA. These results appear to support the hypothesis that high PAH exposure levels may be etiologically associated with the development of esophageal cancer in Linxian.

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