STRUCTURE-DEPENDENT REDUCTION IN DNA I-COMPOUND ADDUCTS BY POLYCHLORINATED DIBENZOFURANS IN FEMALE SPRAGUE-DAWLEY RAT-LIVER Academic Article uri icon

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 g/kg/week or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at 10 g/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 g/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. 1992.

published proceedings

  • CHEMOSPHERE

author list (cited authors)

  • RANDERATH, K., RANDERATH, E., REDDY, R., NARASIMHAN, T. R., WANG, X., & SAFE, S.

citation count

  • 0

complete list of authors

  • RANDERATH, K||RANDERATH, E||REDDY, R||NARASIMHAN, TR||WANG, X||SAFE, S

publication date

  • October 1992