Abstract
The O-demethylation of two antitumor drugs (9-methoxyellipticine and a 1-polyalkylamino-substituted analog) was studied by incubation with liver microsomes from rats and mice. The former drug underwent a cytochrome P1-450-independent biotransformation in mice, as shown by an indiscriminate response from individuals genetically responsive or nonresponsive to induction by 3-methylcholanthrene. On the other hand, the second drug was O-demethylated only by genetically responsive mice after pretreatment by 3-methylcholanthrene. It was also O-demethylated predominantly in rats pretreated with either 3-methylcholanthrene or Aroclor 1254.
MeSH terms
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Alkaloids / metabolism*
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Animals
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Aroclors / pharmacology
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Aryl Hydrocarbon Hydroxylases / genetics*
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Chlorodiphenyl (54% Chlorine)
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Chromatography, High Pressure Liquid
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Cytochrome P-450 Enzyme System / genetics
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Cytochrome P-450 Enzyme System / metabolism*
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Dealkylation
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Ellipticines / metabolism*
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Enzyme Induction / drug effects
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Female
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In Vitro Techniques
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Male
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Mass Spectrometry
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Methylcholanthrene / pharmacology
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Mice
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Mice, Inbred C57BL
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Microsomes, Liver / enzymology
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Phenobarbital / pharmacology
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Phenotype
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Rats
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Rats, Inbred Strains
Substances
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Alkaloids
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Aroclors
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Ellipticines
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Chlorodiphenyl (54% Chlorine)
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Methylcholanthrene
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Cytochrome P-450 Enzyme System
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Aryl Hydrocarbon Hydroxylases
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retelliptine
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9-methoxyellipticine
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Phenobarbital