Piperonyl butoxide and acenaphthylene induce cytochrome P450 1A2 and 1B1 mRNA in aromatic hydrocarbon-responsive receptor knock-out mouse liver.
It has been suggested that acenaphthylene (ACN), piperonyl butoxide (PBO) and other methylenedioxyphenyl (benzodioxole) compounds can function as aromatic hydrocarbon-responsive receptor (AHR)-independent inducers of the cytochrome P450 (CYP) 1A2 in mouse liver. Although much indirect evidence has supported this hypothesis, direct proof was lacking until the present study. PBO and ACN were used to examine the expression of CYP1A1, CYP1A2 and CYP1B1 in mouse liver. These three CYP isozymes are included in the AHR battery of proteins. In this study, AHR knock-out mice were dosed intraperitoneally with PBO (200 mg/kg) or ACN (100 mg/kg). Induction of hepatic CYP1A1 by PBO or ACN was not detected by northern blots. In contrast, both CYP1A2 and CYP1B1 mRNA, constitutively expressed at low levels in this tissue, were induced by each compound in the livers of AHR knock-out mice. In addition, the use of heterogenous nuclear RNA reverse transcription-polymerase chain reaction procedures revealed that the transcriptional activities of CYP1A2 were increased by PBO and ACN treatments. These results show that AHR-independent pathway(s) can be involved in induction of CYP1A2 and CYP1B1.
Ryu
D Y
DY
Department of Toxicology, North Carolina State University, Raleigh 27695, USA.
Levi
P E
PE
Fernandez-Salguero
P
P
Gonzalez
F J
FJ
Hodgson
E
E
D000073:Acenaphthenes / Q000494:pharmacology*; D000199:Actins / Q000096:biosynthesis; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001483:Base Sequence; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D017931:DNA Primers; D015342:DNA Probes; D004790:Enzyme Induction; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010882:Piperonyl Butoxide / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D014158:Transcription, Genetic
D000073:Acenaphthenes; D000199:Actins; D017931:DNA Primers; D015342:DNA Probes; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; C042553:acenaphthylene; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; C585498:Cyp1b1 protein, mouse; D019388:Cytochrome P-450 CYP1A2; D065633:Cytochrome P-450 CYP1B1; D010882:Piperonyl Butoxide