PMID- 10497882
OWN - NLM
STAT- MEDLINE
DCOM- 19991124
LR  - 20190818
IS  - 0300-8177 (Print)
IS  - 0300-8177 (Linking)
VI  - 198
IP  - 1-2
DP  - 1999 Aug
TI  - Evidence for the involvement of the fatty acid and peroxisomal beta-oxidation
      pathways in the inhibition by dehydroepiandrosterone (DHEA) and induction by
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and benz(a)anthracene (BA) of
      cytochrome P4501B1 (CYP1B1) in mouse embryo fibroblasts (C3H10T1/2 cells).
PG  - 89-100
AB  - Treatment of intact C3H10T1/2 cells or microsomes therefrom with
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and benzanthracene (BA) enhanced
      CYP1B1 activity and CYP1B1 expression as revealed by elevations of
      CYP1B1-catalyzed DMBA metabolism, CYP1B1 apoprotein level and CYP1B1 gene
      expression. One hundred microM DHEA caused an 80-90% inhibition of cellular DMBA 
      metabolism without inflicting cell death. Cytosolic glucose-6-phosphate
      dehydrogenase (G6PDH) was also inhibited in DHEA-treated cells, presumably due to
      the inhibition of NADP reduction. In contrast, neither DMBA metabolism nor CYP1B1
      apoprotein was inhibited by DHEA in the microsomes isolated from these cells.
      DHEA (100 microM), TCDD (10 nM) and BA (10 microM) stimulated the activities and 
      increased the apoprotein levels of two peroxisomal enzymes, namely, acyl CoA
      oxidase (ACOX) and acyl CoA hydrolase (ACH2) and also induced the expression of
      CYP1B1 and ACOX genes. Cytosolic fatty acyl-CoA beta-oxidation was also
      stimulated by DHEA, TCDD and BA. In corroboratory experiments, it was found that 
      concomitant with the stimulation of the activity of a key enzyme regulator of
      fatty acid homeostasis, namely, glycerol-3-phosphate dehydrogenase (G3PDH), these
      agents enhanced arachidonic acid (AA) metabolism as judged by the release of [3H]
      from AA into the culture medium. Collectively, these data suggest that DHEA
      mediates the regulation of CYP1B1 and inhibits BA and TCDD-induced
      CYP1B1-catalyzed carcinogen (DMBA) activation in 10T1/2 cells through metabolic
      interactions that involve the activation of the peroxisomal and fatty acid
      beta-oxidation signaling pathways. These results also present evidence for the
      first time, for the possible peroxisomal effects of TCDD and BA which are similar
      to those of DHEA in this mouse embryo fibroblast cell line.
FAU - Ikegwuonu, F I
AU  - Ikegwuonu FI
AD  - Department of Pharmacology, University of Wisconsin, Medical School, Madison,
      USA.
FAU - Jefcoate, C R
AU  - Jefcoate CR
LA  - eng
GR  - CA 16265/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Benz(a)Anthracenes)
RN  - 0 (Fatty Acids)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 459AG36T1B (Dehydroepiandrosterone)
RN  - 57-97-6 (9,10-Dimethyl-1,2-benzanthracene)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - C5PLF6152K (benz(a)anthracene)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (Cyp1b1 protein, mouse)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1B1)
RN  - EC 1.3.3.6 (Acyl-CoA Oxidase)
SB  - IM
MH  - 9,10-Dimethyl-1,2-benzanthracene/metabolism
MH  - Acyl-CoA Oxidase
MH  - Animals
MH  - *Aryl Hydrocarbon Hydroxylases
MH  - Benz(a)Anthracenes/*pharmacology
MH  - Cytochrome P-450 CYP1B1
MH  - Cytochrome P-450 Enzyme System/*biosynthesis/genetics
MH  - Cytosol/enzymology
MH  - Dehydroepiandrosterone/*pharmacology
MH  - Embryo, Mammalian/cytology/drug effects/enzymology
MH  - Enzyme Induction
MH  - Fatty Acids/*metabolism
MH  - Fibroblasts/drug effects/enzymology
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Mice
MH  - Oxidation-Reduction
MH  - Oxidoreductases/genetics
MH  - Peroxisomes/*metabolism
MH  - Polychlorinated Dibenzodioxins/*pharmacology
MH  - Signal Transduction
EDAT- 1999/09/25 00:00
MHDA- 1999/09/25 00:01
CRDT- 1999/09/25 00:00
PHST- 1999/09/25 00:00 [pubmed]
PHST- 1999/09/25 00:01 [medline]
PHST- 1999/09/25 00:00 [entrez]
AID - 10.1023/a:1006954216233 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 1999 Aug;198(1-2):89-100. doi: 10.1023/a:1006954216233.