PMID: 2491914Jan 1, 1989Paper

Influence of metabolic factors on the mutagenic effectiveness of cyclophosphamide in Drosophila melanogaster

Mutation Research
J A Zijlstra, E W Vogel

Abstract

This paper describes the influence of changes in metabolic activity on the in-vivo mutagenic effectiveness of cyclophosphamide in Drosophila melanogaster. A dose-dependent increase in mutagenicity was observed until a plateau value is reached which was increased only slightly after enzyme induction with Aroclor 1254, whereas induction with phenobarbital resulted in a decrease, especially when cyclophosphamide was applied by injection. Treatment of the adult males with inhibitors of the monoamine oxidase (MAO, EC 1.4.3.4), such as iproniazid (Ipr), benzimidazole or tryptamine, led to a marked increase of the mutagenic effectiveness of cyclophosphamide especially in spermatocytes. This indicates the importance of metabolic de-activation processes for the limited mutagenicity of cyclophosphamide in Drosophila. The principal active metabolite of cyclophosphamide, phosphoramide mustard, is extensively de-activated by enzymes that can be inhibited by 1-phenylimidazole (PhI), presumably cytochrome P-450 (EC 1.14.14.1), but not by those blocked by MAO inhibitors. Inhibition of the FAD-containing dimethylaniline monooxygenase (FDMAM, EC 1.14.13.8) by N,N-dimethylbenzylamine (N,N-DMB) resulted in some increase in cyclophosphamide mutagen...Continue Reading

References

Jan 1, 1976·Mutation Research·G R Mohn, J Ellenberger
Mar 1, 1988·Mutation Research·J A Zijlstra, E W Vogel
Oct 1, 1985·Archives of Biochemistry and Biophysics·Y Y Tu, C S Yang
Mar 1, 1984·Chemico-biological Interactions·J A ZijlstraD D Breimer
Dec 8, 1980·Life Sciences·D Y Lai, J C Arcos
Jan 1, 1982·Pharmacology·D M Chambers, G C Jefferson

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