Applications of stable V79-derived cell lines expressing rat cytochromes P4501A1, 1A2, and 2B1.
1. Chinese hamster V79-derived cell lines, stably expressing cytochromes P4501A1, 1A2, and 2B1 activities, were constructed by genetic engineering in continuation of our work to establish a battery of V79 derived cell lines designed to study the metabolism of xenobiotics. 2. Cell lines XEM1 and XEM2, expressing cytochrome P4501A1, were capable of the O-dealkylation of 7-ethoxycoumarin and the hydroxylation of benzo[a]pyrene. 3. Cell lines XEMd.MZ and XEMd.NH, expressing P4501A2, were shown to hydroxylate 17 beta-estradiol and 2-aminofluorene. 4. Cell line SD1, expressing cytochrome P4502B1, was able to hydroxylate testosterone stereo- and regio-specifically at the 16 alpha and 16 beta positions. 5. Cell lines were validated in mutagenicity, cytotoxicity, and metabolism studies employing benzo[a]pyrene, trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene, cyclophosphamide, ifosfamide, and picene. 6. Construction of metabolically-competent V79-derived cell lines be recombinant DNA technology will be a fundamental improvement for the evaluation of the cytotoxic, genotoxic and pharmacological properties of a chemical.
Doehmer
J
J
Johannes Gutenberg-Universität, Mainz, Germany.
Wölfel
C
C
Dogra
S
S
Doehmer
C
C
Seidel
A
A
Platt
K L
KL
Oesch
F
F
Glatt
H R
HR
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics; D001711:Biotransformation; D002460:Cell Line / Q000201:enzymology*; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D003520:Cyclophosphamide / Q000493:pharmacokinetics; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004274:DNA, Recombinant / Q000235:genetics; D004101:Dihydroxydihydrobenzopyrenes / Q000378:metabolism / Q000493:pharmacokinetics; D005822:Genetic Vectors / Q000235:genetics; D006900:Hydroxylation; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D010600:Pharmacology / Q000379:methods; D051381:Rats; D014116:Toxicology / Q000379:methods
D004274:DNA, Recombinant; D004101:Dihydroxydihydrobenzopyrenes; C017228:benzo(a)pyrene 7,8-dihydrodiol; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D003520:Cyclophosphamide; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2