Disease relevance of CYP1A1

• CYP1A1 was strongly induced at intermediate concentrations (0.1 microM or 1.0 microM) of TCB, BP, or BNF, but induction was suppressed by higher concentrations, a response not due to general toxicity; cell viability (trypan blue exclusion) was > 97% with BNF or TCB at up to 10 microM [1].

High impact information on CYP1A1

• In addition, Northern blot analyses indicated the CYP1A1 was not expressed in the adrenal gland, suggesting that only CYP2D16 composed the microsomal 50-kDa band [2].
• The results show that CYP1A1 but not CYP1A2 is strongly induced in mammalian endothelial cells in culture and that CYP1A1 is active in intact cells, although the catalytic rates are low.(ABSTRACT TRUNCATED AT 400 WORDS)[1]
• Cytochrome P4501A1 (CYP1A1) is strongly inducible in vertebrate endothelium in vivo by aryl hydrocarbon receptor (AhR) agonists [Mol. Pharmacol. 36:723-729 (1989); Mol. Pharmacol. 41:1039-1046 (1992)] [1].
• Immunoblotting with monoclonal anti-CYP1A1 and polyclonal anti-CYP1A1 and anti-CYP1A2 antibodies showed that CYP1A1 was induced in cultures exposed to TCDD, TCB, BP, or BNF but was not detectable in untreated or dimethylsulfoxide-exposed cultures [1].
• Mechanism-based inactivation of cytochrome P450 1A1 by N-aralkyl-1-aminobenzotriazoles in guinea pig kidney in vivo and in vitro: minimal effects on metabolism of arachidonic acid by renal P450-dependent monooxygenases [3].

Biological context of CYP1A1

• Mapping of the CYP1A1, SSTR1 and TTF1 genes to pig chromosome 7q refines the porcine-human comparative map [4].
• The amino acid sequence of guinea pig CYP1A1 shared 74-78% identity with those of the other mammalian CYP1A1s [5].
• Guinea pig CYP1A1 cDNA was isolated from a liver cDNA library of guinea pig treated with 3-methylcholanthrene [5].
• Dietary flavonoids modulate PCB-induced oxidative stress, CYP1A1 induction, and AhR-DNA binding activity in vascular endothelial cells [6].
• This study presents full-length cDNA sequences of CYP1A1 and 1A2, in common minke whale (Balaenoptera acutorostrata) from the North Pacific. Both CYP1A1 and CYP1A2 cDNAs had an open reading frame of 516 amino acid residues, and predicted molecular masses were 58.3 kDa and 58.1 kDa, respectively [7].

Anatomical context of CYP1A1

• Western blot analysis of protein expressed by full-length cDNA in COS-1 cells identified CYP1A2 (56 kDa) and CYP1A1 (53 kDa) proteins in corun liver microsomes [8].
• CYP1A1 induction in several organs is clear evidence for successful contaminant mobilization and absorption in the duodenum and subsequent distribution of contaminant into diverse body compartments [9].
• The present finding demonstrates that airborne particulates generated during the frying of beef, fish and pork can induce carcinogen-metabolizing CYP1A1 and CYP1B1 in the human lung-derived cell line CL5 [10].
• Expression of cytochrome P450 1A1, an estrogen hydroxylase, in ovarian granulosa cells is developmentally regulated [11].

Associations of CYP1A1 with chemical compounds

• CYP1A2 transfectants metabolized methoxyresorufin and ethoxyresorufin, while CYP1A1 transfectants metabolized only ethoxyresorufin [8].
• EGCG at 50 muM and quercetin at 100 muM concentrations markedly inhibited CYP1A1 mRNA levels and enzyme activity [6].
• Indole-3-carbinol modulation of hepatic monooxygenases CYP1A1, CYP1A2 and FMO1 in guinea pig, mouse and rabbit [12].
• In PAEC exposed to 0.1 nM TCDD + 10 microM cortisol the level of CYP1A1 protein and the degree of ethoxyresorufin-O-deethylase (EROD) activity induction were 2- to 3-fold greater than with 0.1 nM TCDD alone [13].

Analytical, diagnostic and therapeutic context of CYP1A1

• Molecular cloning of cDNA for guinea pig CYP1A2 comparison with guinea pig CYP1A1 [8].
• However, the quantity of CYP1A1 isoform determined in the D300 group did not differ from that in the F300 group, as revealed by SDS-PAGE and Western blot testing [14].

References