Guengerich F P, Gillam E M, Shimada T
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Crit Rev Toxicol. 1996 Sep;26(5):551-83. doi: 10.3109/10408449609037477.
Bacterial systems have long been of use in toxicology. In addition to providing general models of enzymes and paradigms for biochemistry and molecular biology, they have been adapted to practical genotoxicity assays. More recently, bacteria also have been used in the production of mammalian enzymes of relevance to toxicology. Escherichia coli has been used to express cytochrome P450, NADPH-cytochrome P450 reductase, flavin-containing monooxygenase, glutathione S-transferase, quinone reductase, sulfotransferase, N-acetyltransferase, UDP-glucuronosyl transferase, and epoxide hydrolase enzymes from humans and experimental animals. The expressed enzymes have been utilized in a variety of settings, including coupling with bacterial genotoxicity assays. Another approach has involved expression of mammalian enzymes directly in bacteria for use in genotoxicity systems. Particularly with Salmonella typhimurium. Applications include both the reversion mutagenesis assay and a system using a chimera with an SOS-response indicator and a reporter.
细菌系统长期以来一直用于毒理学研究。除了为生物化学和分子生物学提供酶的通用模型和范例外,它们还被应用于实际的遗传毒性检测。最近,细菌也被用于生产与毒理学相关的哺乳动物酶。大肠杆菌已被用于表达来自人类和实验动物的细胞色素P450、NADPH-细胞色素P450还原酶、含黄素单加氧酶、谷胱甘肽S-转移酶、醌还原酶、磺基转移酶、N-乙酰转移酶、UDP-葡萄糖醛酸基转移酶和环氧化物水解酶。所表达的酶已在多种情况下得到应用,包括与细菌遗传毒性检测相结合。另一种方法是直接在细菌中表达哺乳动物酶,用于遗传毒性系统,特别是在鼠伤寒沙门氏菌中。应用包括回复突变试验和使用带有SOS反应指示剂和报告基因的嵌合体的系统。