Non-random nature of 2-acetylaminofluorene-induced alterations of DNA template capacity

Edward L. Schwartz, J. I. Goodman

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Male rats were fed a diet containing 0.03% (w/w) 2-acetylaminofluorene (AAF) and their hepatic DNA was isolated and transcribed with E. coli RNA polymerase. Ingestion of the carcinogen-containing diet for 4 days substantially reduced the template capacity of the isolated DNA. This reduction in template capacity was due to an apparent decreased RNA chain size (up to 50%), with no significant changes in initiation or re-initiation of RNA synthesis. This premature termination of RNA synthesis was accompanied, in some instances, by a reduced rate of RNA chain elongation. When the rats were returned to a basal diet for 7 days following 4 days of AAF ingestion, template capacity and RNA chain size returned to control values. Fractionation of hepatic chromatin on a glycerol gradient revealed that inhibition of DNA template capacity occurs on portions exhibiting characteristics of expressed, as well as those with characteristics of repressed, segments of the genome. In contrast, the DNA isolated from a small, highly condensed chromatin fraction (15% of total chromatin-DNA) showed no significant reduction in total template capacity. Analysis of the fidelity of RNA synthesis on this DNA template was performed by determining the rate of addition of individual nucleotide triphosphates to a growing RNA chain. Large reductions in the rates of adenosine and uridine polymerization were observed while no changes in guanosine or cytidine polymerization were found. This suggests the presence of functionally significant carcinogen-induced modifications of adenine. The inhibition in the rate of adenosine and uridine polymerization was reversed when the animals were placed on a basal diet after AAF ingestion.

Original languageEnglish (US)
Pages (from-to)1-15
Number of pages15
JournalChemico-Biological Interactions
Volume27
Issue number1
DOIs
StatePublished - 1979
Externally publishedYes

Fingerprint

2-Acetylaminofluorene
RNA
Nutrition
DNA
Polymerization
Diet
Chromatin
Eating
Uridine
Carcinogens
Adenosine
Rats
Cytidine
Guanosine
Liver
Adenine
DNA-Directed RNA Polymerases
Fractionation
Glycerol
Escherichia coli

ASJC Scopus subject areas

  • Toxicology

Cite this

Non-random nature of 2-acetylaminofluorene-induced alterations of DNA template capacity. / Schwartz, Edward L.; Goodman, J. I.

In: Chemico-Biological Interactions, Vol. 27, No. 1, 1979, p. 1-15.

Research output: Contribution to journalArticle

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