Heterologous expression of drug-metabolizing enzymes in cellular and whole animal models

A. P. Simula, M. B. Crichton, Stephen Matthew Black, S. Pemble, H. F.J. Bligh, J. D. Beggs, C. R. Wolf

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

In this report we describe the heterologous expression of glutathione S-transferase (GST) and cytochrome P450 reductase (Red) in E. coli and Salmonella typhimurium. The same expression vectors could be applied to both systems and high levels of catalytically active GST and Red were obtained. Interestingly the level of expression was invariably higher in S. typhimurium. The level of the alpha class GST being up to 20% of the total bacterial protein. A further advantage of the salmonella system is that strains were used which can be applied to mutagenicity tests. This system was validated by demonstrating increasing mutation frequency of halogenated hydrocarbons in strains expressing the GST and increased cytotoxicity of mitomycin C in cells expressing P450 reductase.

Original languageEnglish (US)
Pages (from-to)3-20
Number of pages18
JournalToxicology
Volume82
Issue number1-3
DOIs
StatePublished - Oct 5 1993

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Glutathione Transferase
Animals
Animal Models
Salmonella typhimurium
Salmonella
Enzymes
Halogenated Hydrocarbons
Pharmaceutical Preparations
Mutagenicity Tests
NADPH-Ferrihemoprotein Reductase
Oxidoreductases
Bacterial Proteins
Glutathione Reductase
Mitomycin
Mutation Rate
Cytotoxicity
Escherichia coli
Cells

Keywords

  • Cytochrome P450
  • Glutathione transferases
  • Mutagenicity testing
  • P450 reductase
  • Salmonella typhimurium

ASJC Scopus subject areas

  • Toxicology

Cite this

Simula, A. P., Crichton, M. B., Black, S. M., Pemble, S., Bligh, H. F. J., Beggs, J. D., & Wolf, C. R. (1993). Heterologous expression of drug-metabolizing enzymes in cellular and whole animal models. Toxicology, 82(1-3), 3-20. https://doi.org/10.1016/0300-483X(93)90056-X

Heterologous expression of drug-metabolizing enzymes in cellular and whole animal models. / Simula, A. P.; Crichton, M. B.; Black, Stephen Matthew; Pemble, S.; Bligh, H. F.J.; Beggs, J. D.; Wolf, C. R.

In: Toxicology, Vol. 82, No. 1-3, 05.10.1993, p. 3-20.

Research output: Contribution to journalArticle

Simula, AP, Crichton, MB, Black, SM, Pemble, S, Bligh, HFJ, Beggs, JD & Wolf, CR 1993, 'Heterologous expression of drug-metabolizing enzymes in cellular and whole animal models', Toxicology, vol. 82, no. 1-3, pp. 3-20. https://doi.org/10.1016/0300-483X(93)90056-X
Simula AP, Crichton MB, Black SM, Pemble S, Bligh HFJ, Beggs JD et al. Heterologous expression of drug-metabolizing enzymes in cellular and whole animal models. Toxicology. 1993 Oct 5;82(1-3):3-20. https://doi.org/10.1016/0300-483X(93)90056-X
Simula, A. P. ; Crichton, M. B. ; Black, Stephen Matthew ; Pemble, S. ; Bligh, H. F.J. ; Beggs, J. D. ; Wolf, C. R. / Heterologous expression of drug-metabolizing enzymes in cellular and whole animal models. In: Toxicology. 1993 ; Vol. 82, No. 1-3. pp. 3-20.
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