Human fibroblast chromatin states as effectors of the dna binding characteristics of benzo[a]pyrene anti-7,8-dihydrodiol 9,10-epoxide and two nonalkylating dna-binding molecules

Margaret R. Warner, Philip Iannaccone, William E. Fahl*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Pure populations of mitotic or nonmitotic diploid human fibroblasts (>98% pure) were exposed to [3H)benzo[a)pyrene (CAS: 50-32-8) anti-7,8-dihydrodiol 9,10-epoxide: r-7, t-8 dihydroxy-t-9,10-oxy-7, 8,9,10-tetrahyd robenzo[ a) pyrene (or antidiol- epoxide). In addition, metaphase chromosomes, interphase chromatin, or naked DNA was isolated from the pure cell populations and then titrated to saturation with anti-diol-epoxide, chromomycin A3, or 3,8-diamino-5-ethyl-6-phenylphenanthridinium bromide (ethidium bromide). At saturation, anti-diol-epoxide had covalently modified 1.5% of the total deoxyguanosine residues in naked DNA, and this was reduced to 29 and 15% of this level in saturating the available anti-diol-epoxide-binding sites in chromosomes or chromatin, respectively. A similar hierarchy of accessible binding sites (naked DNA> chromosomes> chromatin) was also observed for the noncovalent interaction of chromomycin A3 or ethidium bromide with the human cell DNA. Deproteinization of the chromosome or chromatin preparations returned the level of drug binding to that seen with naked DNA. The results clarify the association between proteins and DNA in human chromatin and suggest how cell-cycle-dependent changes in DNA-associated proteins or higher-order changes in protein-DNA conformation can act to alter the access of molecules to DNA-binding sites.

Original languageEnglish (US)
Pages (from-to)649-656
Number of pages8
JournalJournal of the National Cancer Institute
Volume77
Issue number3
DOIs
StatePublished - Sep 1986

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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