Factors influencing the binding of N-2-fluorenylacetamide to specific regions of the hepatic genome in vivo in rats.
The initial binding of N-fluorenylacetamide (2-FAA) and its N-hydroxy metabolite N-hydroxyl-N-2-fluorenylacetamide (N-OH-2-FAA) within the hepatic genome and the effect of ingestion of a 2-FAA-containing (0.05% wt/wt) diet on this binding were examined in the male noninbred Sprague-Dawley rat. Ingestion of 2-FAA for 2 weeks reduced the amount of newly bound carcinogen up to 80%. The extent of this decrease was significantly greater in rats treated with a single injection of 2-FAA when compared to one of N-OH-2-FAA. The distribution of carcinogen within the genome was measured after fractionation of chromatin by DNase II digestion followed by selective MgCl2 precipitation. Two hours after a single injection of N-OH-2-FAA, the amount of carcinogen bound per milligram DNA in the presumed template-active chromatin fraction was 16 times that bound to DNA of the presumed template-repressed chromatin fraction. The amount bound to DNA in the nuclease-resistant chromatin was equal to that observed in the DNA of the presumed template-active fraction. Most (85%) of the total bound carcinogen was located on less than 25% of the total DNA. Evaluation of the amount of carcinogen bound to the N-2 or C-8 positions of guanine demonstrated a significant inverse correlation between the amount bound to a DNA fragment and the percent of that binding occurring at the N-2 position. DNA of the repressed chromatin fraction had the largest N-2/C-8 ratio when compared to the ratios seen in both the expressed chromatin and the nuclease-resistant chromatin DNA. Pretreatment of rats with 2-FAA when compared to one of N-OH-2-FAA. The distribution of carcinogen within the genome was measured after fractionation of 66:667-672.
D015073:2-Acetylaminofluorene / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D003851:Deoxyribonucleases; D005796:Genes / Q000187:drug effects; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008274:Magnesium; D015636:Magnesium Chloride; D008297:Male; D051381:Rats
D002843:Chromatin; D015636:Magnesium Chloride; D006881:Hydroxyacetylaminofluorene; D004247:DNA; D015073:2-Acetylaminofluorene; D003851:Deoxyribonucleases; D008274:Magnesium