Title : Induction and inhibition of human cytochrome P4501 by oxygenated polycyclic aromatic hydrocarbons.

Pub. Date : 2016 May 1

PMID : 30090389






8 Functional Relationships(s)
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1 In this study, the effects of 15 environmentally relevant oxy-PAHs on the induction and activity of the CYP1 enzymes were determined in vitro by measuring gene expression levels and enzyme activity. oxy-pahs cytochrome P450 family 1 subfamily A member 1 Homo sapiens
2 We found that nine of the tested oxy-PAHs significantly induced CYP1A1 and CYP1B1 gene expression in human keratinocytes (HaCaT cells) while only five of these also were potent inducers of CYP1-dependent ethoxyresorufin-O-deethylase (EROD) activity suggesting that some of the oxy-PAHs are both activators of AHR signalling and inhibitors of CYP1 function. oxy-pahs cytochrome P450 family 1 subfamily A member 1 Homo sapiens
3 We found that nine of the tested oxy-PAHs significantly induced CYP1A1 and CYP1B1 gene expression in human keratinocytes (HaCaT cells) while only five of these also were potent inducers of CYP1-dependent ethoxyresorufin-O-deethylase (EROD) activity suggesting that some of the oxy-PAHs are both activators of AHR signalling and inhibitors of CYP1 function. oxy-pahs cytochrome P450 family 1 subfamily A member 1 Homo sapiens
4 We found that nine of the tested oxy-PAHs significantly induced CYP1A1 and CYP1B1 gene expression in human keratinocytes (HaCaT cells) while only five of these also were potent inducers of CYP1-dependent ethoxyresorufin-O-deethylase (EROD) activity suggesting that some of the oxy-PAHs are both activators of AHR signalling and inhibitors of CYP1 function. oxy-pahs cytochrome P450 family 1 subfamily A member 1 Homo sapiens
5 Using a recombinant human CYP1A1 enzyme we showed that eleven of the oxy-PAHs potently inhibited enzyme activity with benz[a]anthracene-7,12-quinone (7,12-BAQ) and benzo[a]fluorenone (BFLO) being the most potent inhibitors (IC50 = 0.037 and 0.061 muM, respectively). oxy-pahs cytochrome P450 family 1 subfamily A member 1 Homo sapiens
6 The results showed that oxy-PAHs can interfere with the TCDD-mediated effects leading to reduced CYP1A1 and 1B1 expression and EROD activity. oxy-pahs cytochrome P450 family 1 subfamily A member 1 Homo sapiens
7 These data represent the first demonstration that oxy-PAHs can be potent inhibitors of CYP1 expression and function and make important contributions towards understanding the mechanisms through which oxy-PAHs can contribute to the overall risk of polycyclic aromatic compounds. oxy-pahs cytochrome P450 family 1 subfamily A member 1 Homo sapiens
8 These data represent the first demonstration that oxy-PAHs can be potent inhibitors of CYP1 expression and function and make important contributions towards understanding the mechanisms through which oxy-PAHs can contribute to the overall risk of polycyclic aromatic compounds. oxy-pahs cytochrome P450 family 1 subfamily A member 1 Homo sapiens