Binding of polycyclic and nitropolycyclic aromatic hydrocarbons to specific fractions of rat lung chromatin

Cancer Letters
C E Mitchell, S Akkaraju

Abstract

Carcinogen-induced damage to nuclear matrix DNA, the site of DNA replication and transcription, could have profound effects on gene regulation and mutation. 1,6-Dinitropyrene (1,6-DNP), 1-nitropyrene (1-NP), 6-nitrobenzo[a]pyrene (6-NBP), benzo[a]pyrene (BP) and benzo[a]pyrene diolepoxide (BPDE) were investigated for their abilities to bind to selected regions of DNA in rat lung cell nuclei. Following in vitro exposure to carcinogen, nuclei were fractionated into active chromatin (AC), nuclear matrix (NM) and bulk (low and high salt) chromatin fractions. At an equivalent molar concentration, the highest binding to unfractionated (total) DNA was obtained with BPDE, followed in order by BP, 1,6-DNP, 6-NBP and 1-NP. BPDE, a direct alkylating compound, was bound approximately 18 times higher than the other compounds. All compounds were bound to AC (mononucleosomal DNA approximately 185 bp) and to NM in greater amounts than to bulk DNA. The binding ratios (AC + NM)/(LS + HS) varied from 2 to 21, depending upon the compound. The selective binding to specific DNA regions did not appear to be significantly related to the structures of the parent compounds or to their inferred metabolites. Thus, it appears that selective binding to spec...Continue Reading

References

Jun 1, 1977·The Journal of Cell Biology·R Berezney, D S Coffey
Aug 1, 1988·Toxicology Letters·C E Mitchell
Dec 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·I MellonP C Hanawalt
Nov 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·R C Gupta
Jul 1, 1981·Mutation Research·R MermelsteinH S Rosenkranz
Dec 21, 1982·Biochemistry·H C Smith, R Berezney

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