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Mutagen activation by cDNA-expressed P1450, P3450, and P450a

✍ Scribed by Toshifumi Aoyama; Frank J. Gonzalez; Harry V. Gelboin

Publisher
John Wiley and Sons
Year
1989
Tongue
English
Weight
648 KB
Volume
1
Category
Article
ISSN
0899-1987

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✦ Synopsis

cDNAs for rodent P1450, P3450, and P450a were expressed in the modified vaccinia virus-T7 RNA polymerase system. Each P450 exhibited its appropriate molecular weight and characteristic enzyme activity. Aryl hydrocarbon hydroxylase activity was catalyzed by P1450, acetanilide hydroxylase by P3450, and testosterone 7a-hydroxylase by P450a. Ethoxycoumarin deethylase was exhibited by both P1450 and P3450. Each expressed P450 was also analyzed for its ability to activate 19 carcinogens of diverse classes t o their mutagenic forms. Most notable was the activation of several polycyclic aromatic hydrocarbons by PI and the activation o f acetylaminofluorene, 4-aminobiphenyl, and several heterocyclic amine food pyrolysate products by P3450. P450a, in contrast, showed slight mutagen activation only toward N-hydroxy-2-acetyl aminofluorene. The vaccinia virus-T7 RNA polymerase system described here can express cDNAs for diverse forms o f P450, each of which can then be characterized for substrate and product specificity and for mutagen activation.

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