Cytochrome P-450-mediated O-demethylation of two ellipticine derivatives. Differential effect of the murine Ah locus phenotype.
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.
Roy
M
M
Monsarrat
B
B
Cros
S
S
Lecointe
P
P
Rivalle
C
C
Bisagni
E
E
D000470:Alkaloids / Q000378:metabolism*; D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D020111:Chlorodiphenyl (54% Chlorine); D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D003640:Dealkylation; D004611:Ellipticines / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D013058:Mass Spectrometry; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains
D000470:Alkaloids; D001140:Aroclors; D004611:Ellipticines; D020111:Chlorodiphenyl (54% Chlorine); D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C046349:retelliptine; C001729:9-methoxyellipticine; D010634:Phenobarbital