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首页> 外文期刊>Mutation research. Genetic toxicology testing >MUTAGENICITY OF NITRODIBENZOPYRANONES IN THE SALMONELLA PLATE-INCORPORATION AND MICROSUSPENSION ASSAYS
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MUTAGENICITY OF NITRODIBENZOPYRANONES IN THE SALMONELLA PLATE-INCORPORATION AND MICROSUSPENSION ASSAYS

机译:沙门氏菌平板植入和微悬浮液测定中硝基二苯并吡喃酮的致突变性

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摘要

The mutagenicity of three isomers of nitro-6H-dibenzo[b,d]pyran-6-one (NDBP), 2-NDBP, 3-NDBP and 4-NDBP, was characterized in the plate-incorporation (PI) and microsuspension (MS) assays using Salmonella typhimurium tester strains in the presence or absence of S9 mix. In both assays, all of the NDBPs showed mutagenicity in every strain. In the absence of S9 mix, TA98 was the strain most sensitive to the mutagenicity of NDBPs. The activity of NDBPs was reduced in TA98NR and TA98/1,8-DNP6 strains relative to TA98, suggesting that NDBPs cause frameshift mutation and that nitroreduction by 'classical' nitroreductase and acetylation are significant steps for their metabolic activation. Mutagenic potency of NDBPs in TA98 without S9 mix in the MS assay (2-NDBP 104 300 rev./mu g, 3-NDBP 23 500 rev./mu g, and 4-NDBP 15 300 rev./mu g) was much higher than that in the PI assay (2-NDBP 38 rev./mu g, 3-NDBP 162 rev./mu g, and 4-NDBP 7 rev./mu g). Although additional S9 mix increased the mutagenicity of NDBPs in the PI assay, the mutagenic potency of NDBPs in the MS assay using strains TA98 and TA100 was decreased by the addition of S9 mix. In the PI assay, frameshift and base-substitution activities of both isomers were enhanced by the addition of the pKM101 plasmid, suggesting the induction by these isomers of complex frameshifts (frameshifts with associated base substitutions) in strain TA98. In the PI assay, 2-NDBP generally exhibited more base-substitution than frameshift activity; however, the reverse was true for 3-NDBP. In the MS assay, both isomers exhibited more frameshift than base-substitution activity.
机译:硝基6H-二苯并[b,d]吡喃-6-一(NDBP),2-NDBP,3-NDBP和4-NDBP的三种异构体的致突变性通过板结合(PI)和微悬浮液(在有或没有S9混合物的情况下,使用鼠伤寒沙门氏菌测试菌株进行MS)分析。在这两种测定中,所有NDBP在每个菌株中均显示出致突变性。在没有S9混合物的情况下,TA98是对NDBPs致突变性最敏感的菌株。相对于TA98,TA98NR和TA98 / 1,8-DNP6菌株中NDBP的活性降低,这表明NDBP引起移码突变,“经典”硝基还原酶和乙酰化引起的硝基还原是其代谢激活的重要步骤。在MS分析中(2-NDBP 104300 rev./μg、3-NDBP 23500rev./μg和4-NDBP 15300rev./μg),在没有S9混合的TA98中NDBPs的致突变力很大。高于PI分析(2-NDBP 38转/微克,3-NDBP 162转/微克和4-NDBP 7转/微克)。尽管额外的S9混合物增加了PI测定中NDBP的致突变性,但是通过添加S9混合物降低了使用菌株TA98和TA100在MS测定中NDBP的致突变性。在PI分析中,通过添加pKM101质粒增强了两种异构体的移码和碱基取代活性,这表明这些异构体诱导了TA98菌株中复杂移码(具有相关碱基取代的移码)。在PI分析中,2-NDBP通常表现出比移码活性更多的碱基取代;但是,对于3-NDBP则相反。在MS分析中,两种异构体均比碱基取代活性表现出更多的移码。

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