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Expression of human cytochrome P450 1A1 in DNA repair deficient and proficient human fibroblasts stably transformed with an inducible expression vector |
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| Authors: | States JChristopher; Quan TaiHao; Hines Ronald N; Novak Raymond F; Runge-Morris Melissa |
| Institution: | Center for Molecular Biology Wayne State University, Detroit, MI 48201, USA 1Department of Pharmacology Wayne State University, Detroit, MI 48201, USA 2Institute of Chemical Toxicology Wayne State University, Detroit, MI 48201, USA |
| Abstract: | Cytochromes P450 catalyze the bioactivation of many carcinogens.In particular, cytochrome P450 1A1 (CYP1A1) catalyzes the conversionof polycyclic aromatic hydrocarbons, such as benzoa]pyrene,into potent mutagenic agents. Human skin fibroblasts, both DNArepair deficient (xeroderma pigmentosum group A: XPA) and DNArepair normal have been co-transformed with a chimeric geneconstruct containing human CYP1A1 coding sequences controlledby the cadmium (Cd) ion inducible mouse metallothionein-I promoterand pRSV-NEO, a dominant selectable marker for G418 resistance.Individual G418 resistant colonies were cloned and analyzedfor Cd inducible CYP1A1 activity. Six clones of DNA repair deficientcells and five clones of DNA repair proficient cells have beenisolated which express Cd inducible CYP1A1. Benzoa]pyrene-Aww-7,8-diol (BPD) is cytotoxic in Cd induced CYP1A1 expressing cells.The cytotoxkity can be inhibited by 10 µM |
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