TY - JOUR
T1 - Structure-dependent reduction in DNA I-compound adducts by polychlorinated dibenzofurans in female Sprague-Dawley rat liver
AU - Randerath, K.
AU - Randerath, E.
AU - Reddy, R.
AU - Narasimhan, T. R.
AU - Wang, X.
AU - Safe, S.
N1 - Funding Information:
ACKNOWLEDGEMENTS The financial assistance of the National Institutes of Health (P42-ES04917 and R37-CA32157) is gratefully acknowledged. S. Safe is a Burroughs Wellcome Toxicology Scholar. K. Randerath is the recipient of a DuPont Occupational and Environmental Health grant.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
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U2 - 10.1016/0045-6535(92)90094-8
DO - 10.1016/0045-6535(92)90094-8
M3 - Article
AN - SCOPUS:0027052804
VL - 25
SP - 975
EP - 978
JO - Chemosphere
JF - Chemosphere
SN - 0045-6535
IS - 7-10
ER -