Mutagenesis p. 497 - 504 (1995)
Update date:2022-07-30
Topics:
Ball, L. M.
Stocking, L. M.
Kohan, M. J.
Warren, S. H.
Lewtas, J.
The mutagenic environmental pollutants 2-nitrofluoranthene (2-NFA) and 3-nitrofluoranthene (3-NFA), labelled with 3H and 14C respectively, were incubated with Salmonella typhimurium strain TA98, its nitroreductase-deficient variant TA98NR and its O-acetytransferase-deficient variant TA98/1,8-DNP6, to investigate the activity of these metabolic pathways under conditions approximating those of the Ames assay, hence their contribution to mutagenic potency. 2-Aminofluoranthene (2-AFA) was the major metabolite of 2-NFA (4 μM) in all three TA98 variants, isolated by reverse-phase HPLC and identified by UV-vis and NMR spectroscopy and mass spectrometry. 2-AFA was formed more slowly in TA98NR (65 pmol/h/ml resting phase bacterial broth, 1 to 2E9 bacteria/ml) than in TA98 (295 pmol/h/ml) or TA98/1,8-DNP6 (82 pmol/h/ml). 2-Acetamidofluoranthene (2-AAFA) was also identified in incubations with TA98 (80 pmol/h/ml), TA98NR (21 pmol/h/ml), and TA98/1,8-DNP6 (8 pmol/h/ml). 3-Aminofluoranthene (3-AFA, confirmed by UV-vis and NMR spectroscopy and mass spectrometry) was formed by all three variants from 3-NFA (4 μM): TA98, 1.76 nmol/h/ml; TA98NR, 0.55 nmol/h/ml; TA98/1,8-DNP6, 2.93 nmol/h/ml. 3-Acetamidofluoranthene (3-AAFA) was not detected in any of the variants. 3-AFA and 3-AAFA were less mutagenic than 3-NFA, and required S9 for activation. Mutagenicity of 3-NFA relative to initial nitroreduction rate was similar in TA98 and in TA98NR, but almost 10-fold lower in TA98/1,8-DNP6; hence O-acetylation considerably anhances the mutagenicity of reduction products of 3-NFA. Mutagenicity of 2-NFA relative to initial nitroreduction rate was similar in TA98 and in TA98/1,8-DNP6; the bacterial genotoxicity of 2-NFA is therefore largely independent of O-acetyltransferase activity. Ratios of mutagenicity to nitroreduction rate were similar in TA98 for 2-NFA and 3-NFA; differences in the potency of these isomers arise primarily from their respective suitabilities as substrates for nitroreductase enzymes.
View MoreHangzhou Showland Technology Co., Ltd.
Contact:86-571-88920516
Address:ROOM2118,NO.553,WENSAN ROAD,HANGZHOU,CHINA
Suzhou Wedo Chemicals Co., Ltd.
Contact:86 512 58100425
Address:Zonger Road, DongSha Industry Park , Zhangjiagang, Jiangsu, China
NINGBO YINLIANG FOREIGN TRADE CO., LTD.
Contact:+86-574-87834016 / 87898057
Address:23F NO.666JINYU ROAD,YINGZHOU DISTRICT,NINGBO.CHINA
Linyi Shengxin Pharmaceutical R&D Co., Ltd
Contact:+86-18653953873
Address:West First of Yufeng Road, Yishui County
Changzhou Ruiping Chemical Co., Ltd
website:http://www.wishchem.com
Contact:+86-519-82324280
Address:No.288-1 Huacheng Road, Jintan
Doi:10.1016/S0022-328X(00)84703-8
(1967)Doi:10.1142/S1088424612004525
(2012)Doi:10.1039/c3ra00138e
(2013)Doi:10.1016/j.carres.2013.08.019
(2014)Doi:10.1039/c8cc00847g
(2018)Doi:10.1016/j.peptides.2011.12.003
(2012)