Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1999
Feb;122(2):273-81.
Identification of in vitro cytochrome P450 modulators to detect induction by
prototype inducers in the mallard duckling (Anas platyrhynchos).
Renauld AE, Melancon MJ, Sordillo LM.
USGS Patuxent Wildlife Research Center, Laurel, MD 20708-4041, USA.
Seven modulators of mammalian monooxygenase activity were screened for their
ability to selectively stimulate or inhibit in vitro monooxygenase activities of
hepatic microsomes from mallard ducklings treated with phenobarbital,
beta-naphthoflavone, 3,3',4,4',5-pentachlorobiphenyl or vehicle. Microsomes were
assayed fluorometrically for four monooxygenases: benzyloxy-, ethoxy-, methoxy-,
and pentoxyresorufin-O-dealkylase, in combination with each of the seven
modulators. Four combinations: alpha-naphthoflavone and 2-methylbenzimidazole
with benzyloxyresorufin, and Proadifen with methoxy- and ethoxyresorufin,
respectively, were evaluated further. beta-Naphthoflavone-treated groups were
clearly distinguished from the corn oil vehicle control group by all of the
assays and by the effects of the modulators in three of the four assay/modulator
combinations. Enzyme activities of the phenobarbital and saline groups were
statistically similar (P > or = 0.05) when assayed without modulator added, but
each assay/modulator combination distinguished between these groups. The
PCB-treated group was distinguished from the corn oil vehicle control group only
for BROD activity, with or without the presence of modulator. Graphing of per
cent modulation of BROD activity versus initial BROD activity provided the
clearest distinction between all of the study groups. Identification of these
selective in vitro modulators may improve detection and measurement of low level
cytochrome P450 induction in avian species. Also, both the monooxygenase
activities induced and the impacts of the modulators indicated differences
between mammalian and avian cytochromes P450.
PMID: 10190055 [PubMed - indexed for MEDLINE]
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