PMID: 2506886Jan 1, 1989Paper

Interaction of an ultimate carcinogen, benzo[a]pyrene diol epoxide, with nucleosomal core particles: apparent lack of protection of DNA by histone proteins

Molecular Carcinogenesis
M C MacLeodL K Lew

Abstract

The binding of chemical carcinogens to nuclear macromolecules, especially to DNA, is thought to be central to the initiation of carcinogenesis. Previous studies of the interactions of one such ultimate carcinogen, benzo[a]pyrene diol epoxide (BPDE-I) with nuclei, chromatin and purified DNA, demonstrated that although some BPDE-I-DNA interactions were altered in chromatin, covalent binding to chromatin DNA at saturating chromatin concentrations was quantitatively the same as binding to purified DNA. We have now extended these studies to include the basic subunit of chromatin, the nucleosomal core particle. Association constants for BPDE-I and a nonreactive analogue were determined by absorbance and fluorescence spectroscopy using either core particles or purified DNA and were found to be lower, by a factor of 30, for core particles. One of the major pathways of interaction of BPDE-I with DNA is the catalysis of BPDE-I hydrolysis by the exocyclic amino group of deoxyguanosine in native DNA. This detoxification reaction is inhibited about 30-fold in core particles compared with DNA, consistent with the hypothesis that intercalation is important in this catalytic reaction. In contrast to these findings, at DNA concentrations that a...Continue Reading

References

Dec 1, 1979·Chemico-biological Interactions·A KootstraD E Olins
May 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·J D McGhee, G Felsenfeld
Jan 1, 1977·Annual Review of Biochemistry·R D Kornberg
Dec 1, 1976·Nucleic Acids Research·A L OlinsD E Olins
Aug 6, 1987·Nature·M E HoganR H Austin
Jan 1, 1987·Chemico-biological Interactions·M C MacLeodR M Humphrey
Nov 1, 1988·Carcinogenesis·M C MacLeod, L Lew
Jul 29, 1988·Cell·R H Morse, R T Simpson
Jun 1, 1985·Chemico-biological Interactions·M C MacLeod, K Zachary
Nov 11, 1981·Nucleic Acids Research·P L Jack, P Brookes
Mar 11, 1982·Nucleic Acids Research·J E Arrand, A M Murray
May 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·T Meehan, D M Bond
Oct 11, 1984·Nature·T J RichmondA Klug
Jun 30, 1980·Biochemical and Biophysical Research Communications·A KootstraT J Slaga
Jan 1, 1982·Carcinogenesis·M C MacLeod, J K Selkirk
Jan 18, 1983·Biochemistry·J B ChairesD M Crothers
Oct 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·J WangR H Austin
Jan 1, 1980·Annual Review of Biochemistry·J D McGhee, G Felsenfeld
Jan 1, 1982·Carcinogenesis·M C MacLeodJ K Selkirk
Jan 1, 1981·Analytical Biochemistry·R G Duggleby
Feb 19, 1980·Biochemistry·H M WuD M Crothers

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Citations

Jan 1, 1992·Molecular Carcinogenesis·M Ljungman, P C Hanawalt

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