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Hemoglobin binding of bicyclic aromatic amines
1Walther-Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, Nussbaumstrasse 26, D-80336 München, Germany. Gabriele.Sabbioni@lrz.uni-muenchen.de
Chemical Research in Toxicology
|June 20, 1998
Summary
Researchers investigated aromatic diamine carcinogenicity by measuring hemoglobin adducts in rats. Ortho-substituted diamines with electron-withdrawing groups showed reduced adduct formation, suggesting lower genotoxicity.
Area of Science:
- Toxicology
- Organic Chemistry
- Biochemistry
Background:
- Aromatic diamines like MOCA and MDA are used as curing agents but are mutagenic and carcinogenic.
- Safer substitutes are commercially important.
- Ortho-substitution can reduce mutagenicity, as seen with tetramethylbenzidine.
Purpose of the Study:
- To investigate the biological availability of N-hydroxylamines from ortho-substituted and carcinogenic diamines.
- To correlate hemoglobin adduct formation with carcinogenic potency.
Main Methods:
- Female Wistar rats were dosed with various aromatic diamines.
- Hemoglobin (Hb) adducts were quantified after hydrolysis using HPLC and GC/MS.
- Diamine and monoacetyldiamine levels in Hb were measured.
Main Results:
- MDA, ODA, ethylenedianiline, and TDA formed both diamine and monoacetyldiamine Hb adducts.
- Methylenebis(dimethylaniline), methylenebis(diethylaniline), MOCA, and dapsone formed only diamine Hb adducts.
- Methylenebis(dichloroaniline) showed no Hb binding; ortho-substitution and para-electron-withdrawing groups reduced adduct formation.
Conclusions:
- Reduced Hb adduct formation indicates lower genotoxicity for certain ortho-substituted diamines.
- Hemoglobin adduct levels correlate positively with the carcinogenic potency of bicyclic diamines.