作用机理
Many PAH's induce the expression of cytochrome P450 enzymes, especially CYP1A1, CYP1A2, and CYP1B1, by binding to the aryl hydrocarbon receptor or glycine N-methyltransferase protein. These enzymes metabolize PAH's into their toxic intermediates. The reactive metabolites of PAHs (epoxide intermediates, dihydrodiols, phenols, quinones, and their various combinations) covalently bind to DNA and other cellular macromolecules, initiating mutagenesis and carcinogenesis. (L10, L23, A27, A32)
参考文献
A27 - Uno S, Dragin N, Miller ML, Dalton TP, Gonzalez FJ, Nebert DW: Basal and inducible CYP1 mRNA quantitation and protein localization throughout the mouse gastrointestinal tract. Free Radic Biol Med. 2008 Feb 15;44(4):570-83. Epub 2007 Nov 12. (17997381)
A32 - Padros J, Pelletier E: In vivo formation of (+)-anti-benzo[a]pyrene diol-epoxide-plasma albumin adducts in fish. Mar Environ Res. 2000 Jul-Dec;50(1-5):347-51. (11460716)
A9674 - Roberts EA, Johnson KC, Dippold WG: Ah receptor mediating induction of cytochrome P450IA1 in a novel continuous human liver cell line (Mz-Hep-1). Detection by binding with [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin and relationship to the activity of aryl hydrocarbon hydroxylase. Biochem Pharmacol. 1991 Jul 15;42(3):521-8. (1650214)
A9751 - Harper PA, Prokipcak RD, Bush LE, Golas CL, Okey AB: Detection and characterization of the Ah receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in the human colon adenocarcinoma cell line LS180. Arch Biochem Biophys. 1991 Oct;290(1):27-36. (1654865)
A15114 - Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. (23611293)
L10 - ATSDR - Agency for Toxic Substances and Disease Registry (1995). Toxicological profile for PAHs. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). (http://www.atsdr.cdc.gov/toxprofiles/tp69.html)
L23 - Wikipedia. Benzopyrene. Last Updated 22 January 2009. (http://en.wikipedia.org/wiki/Benzopyrene)