Specificity in interaction of benzo(a)pyrene with nuclear macromolecules: implication of derivatives of two dihydrodiols in protein binding

Journal Article · Sat Nov 01 04:00:00 EST 1980 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.77.11.6396· OSTI ID:6566047

MacLeod, M C ^[1]; Kootstra, A; Mansfield, B K; Slaga, T J; Selkirk, J K

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1. Oak Ridge National Lab., TN

Benzo(a)pyrene (B(a)P), 7,8-dihydroxy-7,8-dihydro-B(a)P, and 9,10-dihydroxy-9,10-dihydro-B(a)P are metabolized by hamster embryo cells to derivatives that bind to nuclear macromolecules. The selectivity for different classes of macromolecules varies depending on the compound analyzed. The ratio of DNA specific activity to protein specific activity (pmol bound/mg of macromolecules) is high (1.51) for 7,8-dihydroxy-7,8-dihydro-B(a)P, extremely low (0.03) for 9,10-dihydroxy-9,10-dihydro-B(a)P, and intermediate (0.26) for B(a)P. Histones H3 and H2A are the major targets of 7,8-dihydroxy-7,8-dihydro-B(a)P; a protein(s) with a mobility similar to that of histone H1 is heavily labeled by 9,10 dihydroxy-9,10-dihydro-B(a)P, with minor labeling of other (nonhistone) bands. The labeling pattern seen with B(a)P is a combination of the patterns seen with the two dihydrodiol metabolites studied. Analysis of the ethyl acetate-soluble metabolites suggests that hamster embryo cells produce 9,10-dihydroxy-7,8-oxy-7,8,9,10-tetrahydro-B(a)P from 9,10-dihydroxy-9,10-dihydro-B(a)P and raise the possibility that this vicinal diol epoxide is an intermediate in the binding of 9,10-dihydroxy-9,10-dihydro-B(a)P to nuclear proteins. The differences seen suggest that factors other than the intrinsic chemical reactivity of the epoxide group are extremely important in the ineraction of potential ultimate carcinogens with biological systems.

• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 6566047
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 77:11; ISSN PNASA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ALCOHOLS
ANIMAL CELLS
ANIMALS
AROMATICS
BENZOPYRENE
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BINDING ENERGY
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
CARCINOGENESIS
CELL CULTURES
CHEMICAL ANALYSIS
COMPARATIVE EVALUATIONS
CONDENSED AROMATICS
DNA
ELECTROPHORESIS
EMBRYONIC CELLS
ENERGY
GLYCOLS
HAMSTERS
HISTONES
HYDROCARBONS
HYDROGEN ISOTOPES
HYDROXY COMPOUNDS
IN VITRO
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
METABOLISM
METABOLITES
MOLECULAR STRUCTURE
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PATHOGENESIS
PROTEINS
QUANTITATIVE CHEMICAL ANALYSIS
RADIOISOTOPES
REACTION KINETICS
RNA
RODENTS
SENSITIVITY
TRITIUM
VERTEBRATES
YEARS LIVING RADIOISOTOPES