Benzo[a]pyrene-diol-epoxide-DNA (BPDE-DNA) adducts were prepared synthetically and subjected to analysis by spectrophotometry, spectrophotofluorimetry and ultra-sensitive-enzyme-linked-radioimmunoassay (USERIA). The extent of DNA modification was originally determined to be 1% (1 adduct in 100 nucleotides) using the method of Santella et al. It was further determined that 1 adduct in 1.4 x 10 to the seventh power nucleotides could be detected using spectrophotofluorimetry (2) and 1 adduct in 2.8 x 10 to the seventh power nucleotides could be detected by USERIA (1). Both of these methods were subsequently applied to the analysis of human DNA samples that were obtained from individuals who were occupationally and/or deliberately (cigarette smoking) exposed to polycyclic aromatic hydrocarbons (PAHs) (1,2). Among a group of coke oven workers, the presence of hydrocarbon-DNA adducts was detected in 31 out of 41 (76%) individuals by spectrophotofluorimetry and 18 out of 27 (67%) by USERIA; among groups of roofers and foundry workers, the presence of hydrocarbon-DNA adducts was detected in 7 out of 28 (25%) and 7 out of 20 (35%) individuals from these respective groups by USERIA. The results further showed that the presence of hydrocarbon-DNA adducts was related to the tobacco smoking habit. However, occupational and other exposures to complex mixtures of PAHs are most usual. Correspondingly complex fluorescence spectra are frequently encountered and it may be that anti-BPDE-DNA antibodies cross-react with related hydrocarbon-DNA adducts. In order to adequately monitor human populations for exposure to PAHs and other related genotoxic chemicals, it will be necessary to design accurate methods for dosimetry based upon those already used to detect the presence of BPDE-DNA adducts in human samples.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Epidemiology And Genetics (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP005435-01
Application #
4692455
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code