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Characterization of benzo[a]pyrene anti-diol epoxide adducts to human histones

Journal Article · · Chemical Research in Toxicology; (United States)
DOI:https://doi.org/10.1021/tx00038a004· OSTI ID:7035622
; ; ; ;  [1]
  1. Massachusetts Institute of Technology, Cambridge, MA (United States)

Nuclei from human lymphoblast cells grown in culture were treated with [7-[sup 14]C]-([+-])-r-7,t-8-dihydroxy-t-9,t-10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE), and the nucleosomal core histones were isolated for adduct studies by cryogenic fluorescence line narrowing spectroscopy. The four core histones H2A, H2B, H3, and H4 were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which yielded each histone free of contamination by the others. Further purification of histones H2A, H2B, and H4 by reversed-phase HPLC also yielded a tetrahydrotetrol of benzo[a]pyrene, indicating that these three histones had some labile adducts. No tetrol was observed upon purification of histone H3. Fluorescence emission spectra of the HPLC-purified histones recorded at 4 K after vibronic excitation into the S[sub 1] state were generally similar. Fluorescence line-narrowed spectra of model compounds formed by reaction of anti-BPDE with acetic acid, ethylenediamine adduct model matched consistently, at different excitation wavelengths, the spectra of the adducted histones. From this it is concluded that the stable human histone adducts of anti-BPDE are formed by reaction with lysine residues and/or the amino groups of the N-termini. 20 refs., 5 figs., 1 tab.

OSTI ID:
7035622
Journal Information:
Chemical Research in Toxicology; (United States), Journal Name: Chemical Research in Toxicology; (United States) Vol. 7:2; ISSN 0893-228X; ISSN CRTOEC
Country of Publication:
United States
Language:
English