The mutagenicity and interactions of 2- and 4-(acetylamino)fluorene with cytochrome P450 and the aromatic hydrocarbon receptor may explain the difference in their carcinogenic potency

1993 ◽  
Vol 6 (4) ◽  
pp. 535-541 ◽  
Author(s):  
Costas Ioannides ◽  
Yen Ling Cheung ◽  
Judith Wilson ◽  
David F. V. Lewis ◽  
Tim J. B. Gray
Keyword(s):  
Cytochrome P450 ◽  
Aromatic Hydrocarbon ◽  
Carcinogenic Potency ◽  
Aromatic Hydrocarbon Receptor ◽  
The Difference

The 2001 Veylien Henderson Award of the Society of Toxicology of Canada. Positive and negative transcriptional regulation of cytochromes P450 by polycyclic aromatic hydrocarbons

2003 ◽  
Vol 81 (1) ◽  
pp. 59-77 ◽  
Author(s):  
David S Riddick ◽  
Chunja Lee ◽  
Anahita Bhathena ◽  
Yoav E Timsit
Keyword(s):  
Growth Hormone ◽  
Transcriptional Regulation ◽  
Cytochrome P450 ◽  
Aromatic Hydrocarbon ◽  
Aromatic Hydrocarbons ◽  
Cytochromes P450 ◽  
Biological Significance ◽  
Male Rats ◽  
Cytochrome P450 1A1 ◽  
Aromatic Hydrocarbon Receptor

Most responses to aromatic hydrocarbons such as 3-methylcholanthrene (MC) and 2,3,7,8-tetrachlorodibenzo-p-dioxin are mediated by the aromatic hydrocarbon receptor (AHR). The AHR regulates induction of drug-metabolizing enzymes such as cytochrome P450 1A1. However, the expression of several genes of biological significance is decreased by these chemicals. We are examining the mechanisms by which aromatic hydrocarbons suppress constitutive hepatic cytochromes P450, especially the male-specific rat liver cytochrome P450 2C11 (CYP2C11), which is regulated by pulsatile growth hormone (GH) secretion. Aromatic hydrocarbons suppress CYP2C11 via a transcriptional mechanism both in vivo and in cultured hepatocytes, and the AHR appears to be involved; however, studies of protein–DNA interactions and reporter genes driven by the CYP2C11 5'-flanking region have not provided a definitive mechanism for this response. MC attenuates the ability of GH to stimulate hepatic CYP2C11 expression in hypophysectomized (hypx) male rats, and this prompted studies of effects of aromatic hydrocarbons on hepatic GH signaling pathways as a novel aspect of endocrine disruption. Our studies with hypx rats also suggest that the hepatic AHR protein is regulated by a pituitary factor(s). The goal of these molecular mechanistic studies is to improve our understanding of how environmental contaminants modulate the expression of genes coding for xenobiotic- and hormone-metabolizing enzymes.Key words: aromatic hydrocarbons, cytochrome P450, aromatic hydrocarbon receptor, growth hormone, transcriptional regulation.

scholarly journals Dioxin-induced CYP1A1 transcription in vivo: the aromatic hydrocarbon receptor mediates transactivation, enhancer-promoter communication, and changes in chromatin structure.

1996 ◽  
Vol 16 (1) ◽  
pp. 430-436 ◽  
Author(s):  
H P Ko ◽  
S T Okino ◽  
Q Ma ◽  
J P Whitlock
Keyword(s):  
Aromatic Hydrocarbon ◽  
Chromatin Structure ◽  
Transcriptional Control ◽  
Control Mechanism ◽  
Terminal Segment ◽  
Transactivation Domain ◽  
Aromatic Hydrocarbon Receptor ◽  
Cyp1a1 Gene ◽  
Induced Changes

We have analyzed the dioxin-inducible transcriptional control mechanism for the mouse CYP1A1 gene in its native chromosomal context. Our genetic and biochemical studies indicate that a C-terminal segment of the aromatic hydrocarbon receptor (AhR) contains latent transactivation capability and communicates the induction signal from enhancer to promoter. Thus, transactivation and enhancer-promoter communication may be congruent functions of AhR. Both functions require heterodimerization between AhR and the AhR nuclear translocator (Arnt). Our findings also indicate that heterodimerization activates AhR's latent transactivation function and silences that of Arnt. Furthermore, removal of Arnt's transactivation domain does not affect dioxin-induced CYP1A1 transcription in vivo. In addition, our studies demonstrate that dioxin-induced changes in chromatin structure occur by different mechanisms at the CYP1A1 enhancer and promoter and that events at an enhancer can be experimentally dissociated from events at the cognate promoter during mechanistic analyses of mammalian transcription in vivo.

Mitochondrial reactive oxygen production is dependent on the aromatic hydrocarbon receptor

2002 ◽  
Vol 33 (9) ◽  
pp. 1268-1278 ◽  
Author(s):  
Albert P Senft ◽  
Timothy P Dalton ◽  
Daniel W Nebert ◽  
Mary Beth Genter ◽  
Alvaro Puga ◽  
...  
Keyword(s):  
Aromatic Hydrocarbon ◽  
Reactive Oxygen ◽  
Oxygen Production ◽  
Aromatic Hydrocarbon Receptor

Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals

10.1038/ng575 ◽  
2001 ◽  
Vol 28 (4) ◽  
pp. 355-360 ◽  
Author(s):  
Tiina Matikainen ◽  
Gloria I. Perez ◽  
Andrea Jurisicova ◽  
James K. Pru ◽  
Jennifer J. Schlezinger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aromatic Hydrocarbon ◽  
Premature Ovarian Failure ◽  
Ovarian Failure ◽  
Environmental Chemicals ◽  
Aromatic Hydrocarbon Receptor ◽  
Bax Gene
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