Factors influencing the binding of n-2-fluorenylacetamide to specific regions of the hepatic genome in vivo in rats

Edward L. Schwartz, W. Emmett Braselton, Jay I. Goodman

Research output: Contribution to journalArticle

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Abstract

The initial binding of N-fluorenylacetamide (2- FAA) and its N-hydroxy metabolite N-hydroxy-N-2-fluorenylacet- amide (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 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.

Original languageEnglish (US)
Pages (from-to)667-672
Number of pages6
JournalJournal of the National Cancer Institute
Volume66
Issue number4
DOIs
StatePublished - 1981
Externally publishedYes

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2-Acetylaminofluorene
Chromatin
Carcinogens
Genome
Liver
DNA
Deoxyribonucleases
Eating
Injections
Magnesium Chloride
Guanine
Sprague Dawley Rats
Digestion
Diet
hydroxide ion

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Factors influencing the binding of n-2-fluorenylacetamide to specific regions of the hepatic genome in vivo in rats. / Schwartz, Edward L.; Braselton, W. Emmett; Goodman, Jay I.

In: Journal of the National Cancer Institute, Vol. 66, No. 4, 1981, p. 667-672.

Research output: Contribution to journalArticle

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abstract = "The initial binding of N-fluorenylacetamide (2- FAA) and its N-hydroxy metabolite N-hydroxy-N-2-fluorenylacet- amide (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 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.",
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