Activation of the tamoxifen derivative metabolite E to form DNA adducts : comparison with the adducts formed by microsomal activation of tamoxifen

(Z)-1,2-Diphenyl-1-(4-hydroxyphenyl)but-1-ene (metabolite E) has been detected in the plasma of patients treated with tamoxifen. We therefore investigated whether the cis/trans isomers of metabolite E can be activated to form DNA adducts detected by 32P postlabeling. Microsomal activation of metabol...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1995-07, Vol.55 (14), p.3012-3015
Main Authors: PONGRACZ, K, PATHAK, D. N, NAKAMURA, T, BURLINGAME, A. L, BODELL, W. J
Format: Article
Language:English
Subjects:
Alkenes - metabolism
Alkenes - pharmacokinetics
Alkenes - pharmacology
Animals
Antineoplastic agents
Benzene Derivatives - pharmacology
Biological and medical sciences
Biotransformation
DNA - drug effects
DNA - metabolism
DNA Adducts - biosynthesis
Female
General aspects
Horseradish Peroxidase - metabolism
Medical sciences
Microsomes, Liver - drug effects
Microsomes, Liver - metabolism
NADP - metabolism
Oxidation-Reduction
Pharmacology. Drug treatments
Phenols - metabolism
Phenols - pharmacokinetics
Phenols - pharmacology
Rats
Tamoxifen - metabolism
Tamoxifen - pharmacokinetics
Tamoxifen - pharmacology
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Summary:(Z)-1,2-Diphenyl-1-(4-hydroxyphenyl)but-1-ene (metabolite E) has been detected in the plasma of patients treated with tamoxifen. We therefore investigated whether the cis/trans isomers of metabolite E can be activated to form DNA adducts detected by 32P postlabeling. Microsomal activation of metabolite E produced two major (a and b) and up to six minor DNA adducts. Activation with horseradish peroxidase or silver(I)oxide produced the same adducts (a and b). Microsomal activation of tamoxifen produced one major (no. 6) and several minor DNA adducts. Rechromatography showed that adducts a and b formed by enzymatic and chemical activation of metabolite E were the same as adducts 9 and 4 produced by microsomal activation of tamoxifen. These results demonstrate that activation of metabolite E can lead to DNA adduct formation.
ISSN:0008-5472
1538-7445