Establishment of a Salmonella tester strain highly sensitive to mutagenic heterocylic amines.
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-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimenthylimidazo[4,5-f]quinoline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-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.
Kamataki
T
T
Division of Pharmacobio-dynamics, Graduate school of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. kamataki@pharm.hokudai.ac.jp
Suzuki
A
A
Kushida
H
H
Iwata
H
H
Watanabe
M
M
Nohmi
T
T
Fujita
K
K
D002384:Catalysis; D002478:Cells, Cultured; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007093:Imidazoles / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics; D009251:NADPH-Ferrihemoprotein Reductase; D010957:Plasmids; D011810:Quinoxalines / Q000633:toxicity*; D012475:Salmonella / Q000187:drug effects* / Q000235:genetics
D007093:Imidazoles; D009153:Mutagens; D011810:Quinoxalines; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D019388:Cytochrome P-450 CYP1A2; D009247:NADH, NADPH Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase