Cyclophosphamide and its metabolite acrolein. Some studies on their porphyrinogenic action in 17 day old chick embryo.
1. Some studies of cyclophosphamide (CP) and its metabolite acrolein in chick embryo liver were carried out in order to investigate the mechanism of the porphyrinogenic action of CP. 2. In vitro and in vivo studies revealed that CP induced but did not activate delta-aminolaevulinic acid (ALA) synthase. 3. Pretreatments with phenobarbital (PB) or SKF-525A did not modify ALA-synthase induction produced by CP. 4. Acrolein administration neither induced ALA-synthase activity nor increased cytochrome P-450 content or led to hepatic porphyrin accumulation. 5. Time course induction of cytochrome P-450 content after administration of CP or PB was similar. 6. The results obtained would indicate that CP is a strong inducer of both ALA-synthase activity and microsomal cytochrome P-450 content in liver of 17 day-old chick embryos and that its porphyrinogenic activity is not mediated by its metabolite acrolein.
Cochón
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AC
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
San Martín de Viale
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LC
Wainstok de Calmanovici
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R
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000171:Acrolein / Q000494:pharmacology*; D000502:Allylisopropylacetamide / Q000494:pharmacology; D000818:Animals; D002642:Chick Embryo / Q000187:drug effects* / Q000378:metabolism; D003520:Cyclophosphamide / Q000378:metabolism / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000187:drug effects* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005865:Gestational Age; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D015394:Molecular Structure; D010634:Phenobarbital / Q000494:pharmacology; D011166:Porphyrins / Q000096:biosynthesis*; D011335:Proadifen
D011166:Porphyrins; D000502:Allylisopropylacetamide; D000171:Acrolein; D003520:Cyclophosphamide; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D000624:5-Aminolevulinate Synthetase; D010634:Phenobarbital