Expression of human cytochrome P450 1A2 in esctierichia colh a new system for biotransformation and genotoxicity studies of chemical carcinogens

M. Kranendonk, P. Mesquita, A. Laires, N. P E Vermeulen, J. Rueff

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Abstract

We describe here the development of BMXl00, a new E. coil K12 tester strain, derived from MX100, a strain which was constructed for mechanistic studies of chemical carcinogens (1). We show that this new tester strain can be used for the stable expression of human P450 1A2 or human P450 1A2 fused to rat liver NADPH P450 reductase. Mutagenicity could be detected of precarcinogens, known to be bioactivated by P450 1A2, namely 2-aminoanthracene (2-AA), aflatoxin B1 (AFB1) and 2-amino-3-methylimidazo(4.5)-f)quinoline ([Q). The mutagenic activity of 2-AA in strain BMXl00 expressing human P450 IA2 and P450 1A2 fused to rat liver P450 reductase was respectively 10 times and 20 times higher as compared with the standard metabolic activation system derived from rat liver (9 fraction). The bioactivation of 2-AA and AFB 1, was respectively 7 and 16 times more efficient when P450 1A2 was expressed fused to the rat reductase. Furthermore, the mutagenicity of 2-AA could be nullified by a known inhibitor of P450 1A2, alfa-naphthoflavone.

Original languageEnglish
JournalFaseb Journal
Volume11
Issue number9
Publication statusPublished - 1997

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