Specificity of interaction between carcinogenic polynuclear aromatic hydrocarbons and nuclear proteins: widespread occurrence of a restricted pattern of histone-binding in intact cells

Conference · Fri Jan 01 04:00:00 EST 1982

OSTI ID:5237384

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

Metabolic activation of benzo(a)pyrene (B(a)P) produces a number of potentially reactive metabolites. The endproducts 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. In hamster embryo cell nuclei treated with (+)-anti-BPDE, two of the histones of the 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 targets. 7,12-dimethylbenz(a)anthracene and 3-methylcholanthrene show the same pattern of histone binding in hamster embryo cells. Treatment of mouse embryo cells with (/sup 3/H)-BPDE results in covalent binding of the hydrocarbon to histones H3 and H2A among the many cellular targets, while histones H2B and H4 are not bound. Similar binding patterns are seen in mouse embryo cells, a permanent murine, fibroblastic cell line, and a human mammary epithelial cell line, T47D, treated with (/sup 3/H)B(a)P. Again, the histones are unevenly labeled, displaying the H3 and H2A pattern. Histone-binding in the human cells may also be mediated by BPDE. Similar BPDE binding patterns were observed in other murine and human cell lines and in primary cultures of murine epidermal epithelial cells. The restriction of histone H2B and H4 binding appears to be general when intact cultured cells are studied. This specificity was not observed in a mixed reconstituted system in which rat liver microsomes were used to activate B(a)P. This finding reinforces reservations concerning the use of microsomal systems to probe the interactions of carcinogens with macromolecules and the relationships of adduct formation with the processes of carcinogenesis. (ERB)

• Research Organization: Oak Ridge National Lab., TN (USA); Tennessee Univ., Oak Ridge (USA). Graduate School of Biomedical Sciences
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 5237384
• Report Number(s): CONF-820439-6; ON: DE82017524
• Country of Publication: United States
• Language: English

Related Subjects

3-METHYLCHOLANTHRENE
550201 -- Biochemistry-- Tracer Techniques
550301 -- Cytology-- Tracer Techniques
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ANIMAL CELLS
AROMATICS
BENZANTHRACENE
BENZOPYRENE
BINDING ENERGY
CELL CONSTITUENTS
CELL CULTURES
CONDENSED AROMATICS
CONNECTIVE TISSUE CELLS
EMBRYONIC CELLS
ENERGY
FIBROBLASTS
HISTONES
HYDROCARBONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
METABOLITES
MICROSOMES
ORGANIC COMPOUNDS
ORGANOIDS
POLYCYCLIC AROMATIC HYDROCARBONS
PROTEINS
SOMATIC CELLS
TRACER TECHNIQUES
TRITIUM COMPOUNDS