Abstract:
:The major pathway of bioactivation of procarcinogenic heterocyclic aromatic amines (HCAs) is cytochrome P450 1A2 (CYP1A2)-catalyzed N-hydroxylation and subsequent esterification by O-acetyltransferase (O-AT). We have previously reported that an umu tester strain, Salmonella typhimurium OY1001/1A2, endogenously coexpressing human CYP1A2 and NADPH-P450 reductase (reductase), is able to detect the genotoxicity of some aromatic amines [Aryal et al., 1999, Mutat Res 442:113-120]. To further enhance the sensitivity of the strain toward HCAs, we developed S. typhimurium OY1002/1A2 by introducing pCW"/1A2:hNPR (a bicistronic construct coexpressing human P450 1A2 and the reductase) and pOA102 (constructed by subcloning the Salmonella O-AT gene in the pOA101-expressing umuC"lacZ gene) in S. typhimurium TA1535. In addition, as an O-AT-deficient strain, we developed the OY1003/1A2 strain by introducing pCW"/1A2:hNPR and pOA101 into O-AT-deficient S. typhimurium TA1535/1,8-DNP. Strains OY1001/1A2, OY1002/1A2, and OY1003/1A2 expressed, respectively, about 150, 120, and 140 nmol CYP1A2/l culture (in whole cells), and respective cytosolic preparations acetylated 15, 125, and > or = 0 nmol isoniazid/min/mg protein as the O-AT activities of cytosolic preparations, respectively. We compared the induction of umuC gene expression as a measure of genotoxicity and observed that the OY1002/1A2 strain was more sensitive than OY1001/1A2 strain toward the genotoxicity of 2-amino-1,4-dimethylimidazo[4,5-f]quinol ine(MeIQ), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ),2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MeIQx),2-aminoanthracene, 2-amino-6-methyldipyrido[1,2-a::3,2'-d]i midazole,3-amino-1, 4-dimethyl-5H-pyrido[4,3-b]indole, and 3-amino-1-methyl-5H-pyrido[4, 3-a]indole. However, the genotoxicity of MeIQ, IQ, and MeIQx was not detected with the OY1003/1A2 strain. These results indicate that the newly developed strain OY1002/1A2 can be employed in detecting potential genotoxic aromatic amines requiring bioactivation by CYP1A2 and O-acetyltransferase.
journal_name
Environ Mol Mutagenjournal_title
Environmental and molecular mutagenesisauthors
Aryal P,Terashita T,Guengerich FP,Shimada T,Oda Ydoi
10.1002/1098-2280(2000)36:2<121::aid-em6>3.0.co;2-subject
Has Abstractpub_date
2000-01-01 00:00:00pages
121-6issue
2eissn
0893-6692issn
1098-2280pii
10.1002/1098-2280(2000)36:2<121::AID-EM6>3.0.CO;2-journal_volume
36pub_type
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,多中心研究
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更新日期:2001-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20003
更新日期:2004-01-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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journal_title:Environmental and molecular mutagenesis
pub_type: 历史文章,杂志文章
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22007
更新日期:2016-05-01 00:00:00
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journal_title:Environmental and molecular mutagenesis
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
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journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
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更新日期:2015-01-01 00:00:00
abstract::Peripheral lymphocytes from Taiwanese women (n = 35) exposed to polychlorinated aromatic hydrocarbons and from matched controls (n = 24) were assessed for the levels of sister chromatid exchanges (SCEs) after a 72-hour incubation of whole blood in the presence or absence of alpha-naphthoflavone (ANF) and for chromosom...
journal_title:Environmental and molecular mutagenesis
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更新日期:1988-01-01 00:00:00