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Abstract
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 17β-estradiol and 2-aminofluorene.
4. Cell line SD1, expressing cytochrome P4502B1, was able to hydroxylate testosterone stereo- and regio-specifically at the 16α and 16β 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, cyclophos-phamide, 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.