Specificity of Interaction between Carcinogenic Polynuclear Aromatic Hydrocarbons and Nuclear Proteins: Widespread Occurrence of a Restricted Pattern of Histone Binding in Intact Cells

M. C. MacLeod, J. C. Pelling, T. J. Slaga, P. A. Noghrei-Nikbakht, B. K. Mansfield, J. K. Selkirk

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The first steps in the induction of malignancy by chemical carcinogens involve covalent interactions with cellular macromolecules. For the widespread environmental contaminant benzo[a] pyrene (B[a]P), metabolic activation by cellular enzymes produces a number of potentially reactive metabolites. The end products of one metabolic pathway, 7,8-dihydroxy-9,10-oxy-7,8,9,10 tetrahydro-B[a]P (BPDE), are responsible for essentially all DNA adduct formation in animal cells treated with B[a]P, and a particular stereoisomer, designated (+)-anti-BPDE is thought to be the ultimate carcinogenic derivative of B[a]P. It has been shown that in hamster embryo cell nuclei treated with (+)-anti-BPDE, two of the histones of nucleosomal core, H3 and H2A are covalently modified, while the remaining core histones—H4 and H2B—are essentially unmodified. All four purified core histones, however, serve as the targets for (+)-anti-BPDE in vitro.

Original languageEnglish (US)
Pages (from-to)111-116
Number of pages6
JournalProgress in nucleic acid research and molecular biology
Volume29
Issue numberC
DOIs
StatePublished - Jan 1 1983

ASJC Scopus subject areas

  • Molecular Biology

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