Establishment of a Salmonella tester strain highly sensitive to mutagenic heterocylic amines. |
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Authors: | T Kamataki A Suzuki H Kushida H Iwata M Watanabe T Nohmi K Fujita |
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Institution: | Division of Pharmacobio-dynamics, Graduate school of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. kamataki@pharm.hokudai.ac.jp |
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Abstract: | A co-expression plasmid (p1A2OR) carrying human CYP1A2 and NADPH-P450 reductase cDNAs and an expression plasmid (pOAT) carrying Salmonella TA1538/ARO cells. The CYP and OAT expressed in the Salmonella cells showed catalytic activity. The TA1538/ARO strain exhibited high sensitivity to heterocyclic amines (HCAs) such as 2-amino-3,4-dimethylimidazo4,5-f]quinoline (MeIQ), 2-amino-3-methylimidazo4,5-f]quinoline (IQ), 2-amino-3,8-dimenthylimidazo4,5-f]quinoline (MeIQx), 2-amino-1-methyl-6-phenylimidazo4,5-b]pyridine (PhIP) as compared with the parent Ames tester strain TA1538. It is suggested that the intracellular expression of drug-metabolising enzymes makes the Salmonella cells highly sensitive to the HCAs. |
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