Structure-dependent reduction in DNA I-compound adducts by polychlorinated dibenzofurans in female Sprague-Dawley rat liver

K. Randerath, E. Randerath, R. Reddy, T. R. Narasimhan, X. Wang, S. Safe

Research output: Contribution to journalArticle

Abstract

The effects of polychlorinated dibenzofurans (PCDFs) on hepatic I-compound DNA adducts in female Sprague-Dawley rats were determined at 2 dose levels. In the first experiments, rats (4 per group) were treated with each of 3 polychlorinated dibenzofuran (PCDF) congeners at 20 μg/kg/week or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at 10 μg/kg/week for 4 weeks. Effects on total I-compound levels when compared with age-matched control animals (corn oil) were as follows: control (116) > 1,2,4,7,8-pentachlorodibenzofuran (PeCDF) (112) > 1,2,3,7,8-PeCDF (93) > 2,3,4,7,8-PeCDF (91) > TCDD (72) where the numbers in parentheses were the number of I-compounds in 109 DNA nucleotides. In the second experiment, rats (5 per group) were treated with each of the congeners at a higher dose of 100 μg/kg/week for 4 weeks. The effects were as follows: control (123) ≈ 1,2,4,7,8-PeCDF (125) > 1,2,3,7,8-PeCDF (98) > 2,3,4,7,8-PeCDF (75) ≈ 2,3,4,6,7,8-hexachlorodibenzofuran (HCDF) (75). The active compounds (1,2,3,7,8-PeCDF, 2,3,4,7,8-PeCDF and 2,3,4,6,7,8-HCDF) were those that exhibited high cytosolic Ah receptor binding affinities (1.5 - 7.5 × 10-8 M) and were also potent AHH inducers. The inactive compound (1,2,4,7,8-PeCDF) was less active in the receptor binding and enzyme induction assays. The results showed that there was a structure-dependent correlation between the Ah receptor agonist activity of a congener and its potency to reduce I-compounds in female Sprague-Dawley rat liver.

Original languageEnglish (US)
Pages (from-to)975-978
Number of pages4
JournalChemosphere
Volume25
Issue number7-10
DOIs
StatePublished - 1992

ASJC Scopus subject areas

  • Environmental Engineering
  • Environmental Chemistry
  • Chemistry(all)
  • Pollution
  • Health, Toxicology and Mutagenesis

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