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DOI10.1002/em.21737
Dose-response analysis of bromate-induced DNA damage and mutagenicity is consistent with low-dose linear, nonthreshold processes
Spassova, Maria A.1; Miller, David J.1; Eastmond, David A.2; Nikolova, Nadejda S.3; Vulimiri, Suryanarayana V.1; Caldwell, Jane1; Chen, Chao1; White, Paul D.1
发表日期2013
ISSN0893-6692
卷号54期号:1页码:19-35
英文摘要

Mutagenic agents have long been inferred to act through low-dose linear, nonthreshold processes. However, there is debate about this assumption, with various studies interpreting datasets as showing thresholds for DNA damage and mutation. We have applied rigorous statistical analyses to investigate the shape of dose-response relationships for a series of in vitro and in vivo genotoxicity studies using potassium bromate (KBrO3), a water ozonation byproduct that is bioactivated to a reactive species causing oxidative damage to DNA. We analyzed studies of KBrO3 genotoxicity where no-effect/threshold levels were reported as well as other representative datasets. In all cases, the data were consistent with low-dose linear models. In the majority of cases, the data were fit either by a linear (straight line) model or a model which was linear at low doses and showed a saturation-like downward curvature at high doses. Other datasets with apparent upward curvature were still adequately represented by models that were linear at low dose. Sensitivity analysis of datasets showing upward curvature revealed that both low-dose linear and nonlinear models provide adequate fits. Additionally, a simple biochemical model of selected key processes in bromate-induced DNA damage was developed and illustrated a situation where response for early primary events suggested an apparent threshold while downstream events were linear. Overall, the statistical analyses of DNA damage and mutations induced by KBrO3 are consistent with a low-dose linear response and do not provide convincing evidence for the presence of a threshold. Environ. Mol. Mutagen., 2013. (c) 2012 Wiley Periodicals, Inc.


英文关键词dose-response;bromate;genotoxicity;reactive oxygen species;low-dose linearity
语种英语
WOS记录号WOS:000312991300003
来源期刊ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
来源机构美国环保署
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/59065
作者单位1.US EPA, NCEA, ORD, Washington, DC 20460 USA;
2.Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA;
3.Langley High Sch, Mclean, VA USA
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GB/T 7714
Spassova, Maria A.,Miller, David J.,Eastmond, David A.,et al. Dose-response analysis of bromate-induced DNA damage and mutagenicity is consistent with low-dose linear, nonthreshold processes[J]. 美国环保署,2013,54(1):19-35.
APA Spassova, Maria A..,Miller, David J..,Eastmond, David A..,Nikolova, Nadejda S..,Vulimiri, Suryanarayana V..,...&White, Paul D..(2013).Dose-response analysis of bromate-induced DNA damage and mutagenicity is consistent with low-dose linear, nonthreshold processes.ENVIRONMENTAL AND MOLECULAR MUTAGENESIS,54(1),19-35.
MLA Spassova, Maria A.,et al."Dose-response analysis of bromate-induced DNA damage and mutagenicity is consistent with low-dose linear, nonthreshold processes".ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 54.1(2013):19-35.
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