PMID- 9973187
OWN - NLM
STAT- MEDLINE
DCOM- 19990212
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 56
IP  - 12
DP  - 1998 Dec 15
TI  - Methoxyresorufin: an inappropriate substrate for CYP1A2 in the mouse.
PG  - 1657-60
AB  - Hepatic microsomes derived from Cypla2(-/-) knockout (KO) and parental strains of 
      mice, C57BL/6N and 129Sv, were used to examine the specificity of 
      methoxyresorufin and acetanilide as substrates for CYP1A2 activity. In addition, 
      animals from each group were exposed to CYP1-inducing compounds. As expected, 
      microsomes from untreated 1a2 KO mice did not have immunodetectable CYP1A2 
      protein; however, methoxyresorufin-O-demethylase (MROD, 25.5+/-6.1 pmol/min/mg 
      protein) and acetanilide-4-hydroxylation (ACOH, 0.64+/-0.04 nmol/min/mg protein) 
      activities were still present. Furthermore, induction of 
      ethoxyresorufin-O-deethylase (EROD) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 
      in 1a2 KO mice was accompanied by a greater than 70-fold increase in MROD 
      activity. In contrast, ACOH was only induced 2-fold by TCDD. As with 1a2 KO mice, 
      the parental strains exposed to TCDD or 2,3,4,7,8-pentachlorodibenzofuran 
      (4-PeCDF) showed substantial EROD and MROD induction, whereas ACOH activity was 
      induced to a lesser degree. PCB153 (2,2',4,4',5,5'-hexachlorobiphenyl) resulted 
      in low levels of both EROD and MROD induction. Results indicate that both 
      substrates are subject to metabolism by non-CYP1A2 sources, and the apparent 
      contribution of CYP1A1 activity to methoxyresorufin metabolism makes MROD 
      unsuitable for differentiating CYP1A1 and CYP1A2 activities in the mouse.
FAU - Hamm, J T
AU  - Hamm JT
AD  - Curriculum in Toxicology, University of North Carolina, Chapel Hill 27599-7270, 
      USA. hamm.jonathan@epamail.epa.gov
FAU - Ross, D G
AU  - Ross DG
FAU - Richardson, V M
AU  - Richardson VM
FAU - Diliberto, J J
AU  - Diliberto JJ
FAU - Birnbaum, L S
AU  - Birnbaum LS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Benzofurans)
RN  - 0 (Oxazines)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 5725-89-3 (7-methoxyresorufin)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.- (methoxyresorufin-O-demethylase)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
RN  - EC 1.14.14.1 (acetanilide hydroxylase)
RN  - U4C2RV3124 (2,3,4,7,8-pentachlorodibenzofuran)
RN  - ZRU0C9E32O (2,4,5,2',4',5'-hexachlorobiphenyl)
SB  - IM
MH  - Animals
MH  - Aryl Hydrocarbon Hydroxylases/biosynthesis/metabolism
MH  - Benzofurans
MH  - Cytochrome P-450 CYP1A1/biosynthesis/metabolism
MH  - Cytochrome P-450 CYP1A2/biosynthesis/*metabolism
MH  - Cytochrome P-450 Enzyme System/biosynthesis/metabolism
MH  - Enzyme Induction
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Microsomes, Liver/drug effects/*enzymology
MH  - Oxazines/*metabolism
MH  - Oxidoreductases/biosynthesis/metabolism
MH  - Polychlorinated Biphenyls
MH  - Polychlorinated Dibenzodioxins
MH  - Substrate Specificity
EDAT- 1999/02/11 00:00
MHDA- 1999/02/11 00:01
CRDT- 1999/02/11 00:00
PHST- 1999/02/11 00:00 [pubmed]
PHST- 1999/02/11 00:01 [medline]
PHST- 1999/02/11 00:00 [entrez]
AID - S0006-2952(98)00241-X [pii]
AID - 10.1016/s0006-2952(98)00241-x [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1998 Dec 15;56(12):1657-60. doi: 
      10.1016/s0006-2952(98)00241-x.