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Title: Comparison of ethylene, propylene and styrene 7,8-oxide in vitro adduct formation on N-terminal valine in human haemoglobin and on N-7-guanine in human DNA
Authors: Pauwels, W ×
Veulemans, Hendrik #
Issue Date: Sep-1998
Publisher: Elsevier science bv
Series Title: Mutation research-genetic toxicology and environmental mutagenesis vol:418 issue:1 pages:21-33
Abstract: Epoxides react at various nucleophilic sites in macromolecules such as haemoglobin and DNA. To study the reaction rate constants of ethylene oxide (EO), propylene oxide (PO) and styrene 7,8-oxide (SO) towards two of these positions, i.e., the N-terminal valine in haemoglobin and N-7-guanine in DNA was the central aim of this investigation. These two reactive sites are the most studied haemoglobin and DNA adducts, respectively. Further attention, therefore, was also paid to the applicability in vivo of the in vitro determined reaction constants. The determination of the second-order rate constants between EO and PO and N-terminal valine in Hb [2.7 1 (mol Hb h)(-1) and 1.0 1(mol Hb h)(-1), respectively] were consistent with the literature values. The constants for the reaction with N-7-guanine [16 x 10(-3) 1 (mol DNA nucleotide h)(-1) and 7.7 x 10(-3) 1 (mol DNA nucleotide h)(-1), respectively] were lower than previously published values, probably due to differences in the methodology used. The use of the in vitro obtained values to model the in vivo situation lead to a consistent picture for EO and PO. In contrast, for SO the in vitro ratio between the adduct formation on N-terminal valine [1.5 1 (mol Hb h)(-1)] and N-7-guanine [0.71 X 10(-3) 1 (mol DNA nucleotide h)(-1)] was about two orders of magnitude greater than for the in vivo situation. This was probably due to a lower than expected reactivity of SO towards N-terminal valine in vivo. Further research is needed to elucidate whether the use of SO in vitro, contrasting with the in vivo experiments in which SO was metabolically formed from styrene, could entail an explanation for this discrepancy. Concerning the methodological part, the use of dipeptide standards to replace the alkylated globins as standard lead to an improvement of the method. Especially the commercial availability of the standards, their stability and accurately known adduct content will make them to the standards of choice in the future. (C) 1998 Elsevier Science B.V. All rights reserved.
ISSN: 0027-5107
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Environment and Health - miscellaneous
Occupational, Environmental and Insurance Medicine (-)
× corresponding author
# (joint) last author

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