Studies on the binding of B(a)P diol epoxide to DNA and chromatin

Conference · Sun Jan 01 04:00:00 EST 1978

OSTI ID:6632024

Kootstra, A.; Slaga, T. J.; Olins, D. E.

The data strongly suggest that the interaction of B(a)P diol epoxide (anti) with free DNA or chromosomal DNA involved, apart from covalent binding, intercalation of the covalent and non-covalent bound carcinogen, and that in the case of chromatin or mononucleosomes, intercalation appeared to be decreased. This decrease may be a function of changes in DNA conformation, steric hindrance, or both due to the presence of chromosomal proteins. Furthermore in the presence of a competing nucleophile such as cysteine, the covalent binding of B(a)P diol epoxide could be greatly diminished and the data suggest that little if any non-covalent association occurred in chromatin. Analysis of the distribution of the carcinogen with respect to chromosomal components revealed that most of the adducts were associated with chromosomal DNA and that the internucleosomal DNA contained 3 to 4 times more carcinogen than nucleosomal DNA. Reconstitution of labeled chromatin showed that removal of the very lysine-rich histones by 0.65 M NaCl did not affect the distribution of the carcinogen, while complete dissociation using 2.0 M NaCl and reassociation revealed randomization of the bound carcinogen. The reconstitution experiments showed that the presence of carcinogen did not interfere with the reassociation of histones to DNA, and that B(a)P diol epoxide could be used to evaluate the fidelity of reconstituted chromatin in vitro.

• Research Organization: Oak Ridge National Lab., TN (USA); Tennessee Univ., Oak Ridge (USA). School of Biomedical Sciences
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 6632024
• Report Number(s): CONF-781039-5
• Country of Publication: United States
• Language: English

Related Subjects

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
AMINES
AROMATICS
BENZOPYRENE
CHEMICAL BONDS
CHROMATIN
CONDENSED AROMATICS
CONFIGURATION INTERACTION
DNA
DRUGS
EPOXIDES
GLYCOLS
HISTONES
HYDROCARBONS
HYDROXY COMPOUNDS
IN VITRO
MEA
METABOLITES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RESPONSE MODIFYING FACTORS
STEREOCHEMISTRY
THIOLS