Interaction of (+/-)-7r,8t-dihydroxy-9t,10t-oxy-7,8,9,10-tetrahydrobenzo[a]pyre ne with purified rat liver chromatin.
Previous studies have shown that in addition to serving as a target for covalent adduct formation, purified DNA catalyzes the detoxification of (+/-)-7r,8t-dihydroxy-9t,10t-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). To begin to relate these in vitro findings with the processes important in carcinogenesis in vivo, we have prepared native chromatin from rat liver nuclei and analyzed its interactions with BPDE. Using several different methods to follow the hydrolysis of BPDE, we find the ability of chromatin to catalyse this detoxification is severely reduced relative to purified DNA. The rate of formation of covalent adducts is also reduced, although the final level of modification is almost the same in chromatin and purified DNA. The difference in rates could be an important in vivo protection mechanism, especially in the presence of competing nucleophiles, e.g.-SH compounds. In addition, non-covalent, physical binding to chromatin is altered, both quantitatively and qualitatively, compared with purified DNA. The specificity of covalent binding of BPDE to histone proteins in chromatin is identical to the specificity found in intact nuclei.
L
L
Dock
M C
MC
MacLeod
D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006868:Hydrolysis; D008099:Liver / Q000648:ultrastructure*; D008297:Male; D008433:Mathematics; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D001580:Benzopyrenes; D002843:Chromatin; C039385:7,8-dihydroxy-9,10-epoxy-8-methyl-7,8,9,10-tetrahydrobenzo(a)pyrene; D004247:DNA