HETEROLOGOUS EXPRESSION OF DRUG-METABOLIZING-ENZYMES IN CELLULAR AND WHOLE ANIMAL-MODELS

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 we re obtained. Interestingly the level of expression was invariably high er 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 a nd increased cytotoxicity of mitomycin C in cells expressing P450 redu ctase.