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Evidence for the metabolism of mitozantrone by microsomal glutathione transferases and 3-methylcholanthrene-inducible glucuronosyl transferases.

Abstract：

:The metabolism of mitozantrone, a chemotherapeutic agent used in the treatment of breast cancer, has been studied in vitro using rat liver subcellular fractions. This compound would appear to be metabolized by two interesting pathways. One involves conjugation with glucuronic acid, catalyzed most effectively by a 3-methylcholanthrene-inducible glucuronosyl transferase. The other pathway appears to be a glutathione conjugation reaction which requires prior metabolism by cytochrome P-450. The reaction with glutathione appears to be enzymatic as 1-chloro-2,4-dinitrobenzene was a potent inhibitor of this reaction. Liver cytosol did not enhance the microsomal rate of glutathione-conjugate formation, suggesting an important role for the microsomal glutathione transferases in the disposition of this compound. The relationship between these reactions and the mode of action of mitozantrone is discussed.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Wolf CR,Macpherson JS,Smyth JF

doi

10.1016/0006-2952(86)90127-9

subject

Has Abstract

pub_date

1986-05-01 00:00:00

pages

1577-81

issue

9

eissn

0006-2952

issn

1873-2968

pii

0006-2952(86)90127-9

journal_volume

35

pub_type

杂志文章

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