PMID- 8960375
OWN - NLM
STAT- MEDLINE
DCOM- 19970311
LR  - 20101118
IS  - 1431-6730 (Print)
IS  - 1431-6730 (Linking)
VI  - 377
IP  - 11
DP  - 1996 Nov
TI  - Interactions of procarcinogenic heterocyclic amines and indolocarbazoles with the 
      dioxin receptor.
PG  - 741-62
AB  - Cooking of protein-rich food generates procarcinogenic heterocyclic aromatic 
      amines (HCA) in amounts that range in the part per billion levels. HCA have been 
      reported to induce xenobiotic metabolizing enzymes of the cytochrome P450 1A 
      (CYP1A) subfamily, most notably the CYP1A2 isoform. The regulator mechanism of 
      the CYP1A induction by HCA is, however, unclear. Studies in vivo in rats and in 
      primary hepatocyte cultures revealed "that MelQx induced both CYP1A1/1A2 proteins 
      and the corresponding catalytic activities. In contrast to previous studies, no 
      preferential induction of CYP1A2 was observed in the present study. CYP1A1 and 
      CYP1A2 are target genes of the intracellular dioxin receptor. This receptor 
      interacts with xenobiotic response elements (XREs) of target promoters upon 
      binding the environmental pollutant dioxin or related compounds. HCA exhibited 
      capacity to activate the dioxin receptor to a form which interacts with XRE in 
      vitro. Taken together, these results suggest that MelQx regulates both CYP1A 
      isozymes by the same mechanism involving the dioxin receptor. Another group of 
      putative dioxin receptor ligands of dietary orgin are the indolocarbazoles, which 
      are produced in vivo from precursor molecules in cruciferous plants. 
      Indolocarbazoles potently regulated gene expression of a reporter gene driven by 
      a minimal XRE in both mouse and human hepatoma cells. The indolocarbazole-induced 
      human receptor appeared to form more stable complexes with XRE in vitro relative 
      to those generated by the dioxin-activated receptor. This study indicates that 
      the HCA and the indolocarbazoles both represent distinct classes of dietary 
      dioxin receptor agonists.
FAU - Kleman, M
AU  - Kleman M
AD  - Dept of Medical Nutrition, Novum, Huddinge, Sweden.
FAU - Gustafsson, J A
AU  - Gustafsson JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Germany
TA  - Biol Chem
JT  - Biological chemistry
JID - 9700112
RN  - 0 (Amines)
RN  - 0 (Carbazoles)
RN  - 0 (Carcinogens)
RN  - 0 (Heterocyclic Compounds)
RN  - 0 (Indoles)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
SB  - IM
MH  - Amines/*metabolism
MH  - Animals
MH  - Biotransformation
MH  - Carbazoles/*metabolism
MH  - Carcinogens/*metabolism
MH  - Cooking
MH  - Cytochrome P-450 CYP1A1/metabolism
MH  - Cytochrome P-450 CYP1A2/metabolism
MH  - Diet
MH  - Heterocyclic Compounds/*metabolism
MH  - Humans
MH  - Indoles/*metabolism
MH  - Liver/metabolism
MH  - Mice
MH  - Rats
MH  - Receptors, Aryl Hydrocarbon/*metabolism
MH  - Risk Factors
MH  - Structure-Activity Relationship
RF  - 270
EDAT- 1996/11/01 00:00
MHDA- 1996/11/01 00:01
CRDT- 1996/11/01 00:00
PHST- 1996/11/01 00:00 [pubmed]
PHST- 1996/11/01 00:01 [medline]
PHST- 1996/11/01 00:00 [entrez]
PST - ppublish
SO  - Biol Chem. 1996 Nov;377(11):741-62.