Investigating Mechanisms for Non-linear Genotoxic Responses, and Analysing Their Effects in Binary Combination
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- Johnson George E.
- Institute of Life Science, College of Medicine, Swansea University
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- Zaïr Zoulikha M.
- Institute of Life Science, College of Medicine, Swansea University
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- Bodger Owen G.
- Institute of Life Science, College of Medicine, Swansea University
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- Lewis Paul D.
- Institute of Life Science, College of Medicine, Swansea University
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- Rees Ben J.
- Institute of Life Science, College of Medicine, Swansea University
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- Verma Jatin R.
- Institute of Life Science, College of Medicine, Swansea University
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- Thomas Adam D.
- Institute of Life Science, College of Medicine, Swansea University
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- Doak Shareen H.
- Institute of Life Science, College of Medicine, Swansea University
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- Jenkins Gareth J. S.
- Institute of Life Science, College of Medicine, Swansea University
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抄録
A recent shift by the scientific and regulatory community, towards accepting the existence of non-linear dose responses for certain DNA reactive genotoxic agents, has unveiled a myriad of questions regarding their biological basis. The mechanisms responsible for ‘genotoxic tolerance’ at low doses are wide ranging but poorly understood, yet this information is essential when analysing non-linear dose responses for hazard and risk assessment. For DNA reactive genotoxins, non-linear dose responses can arise from many different biological mechanisms, including DNA repair. Recent work from our group explored the contributory role of DNA repair to nonlinear genotoxic dose responses, in human cells exposed alkylating agents. Here we discuss the involvement of the repair enzymes methylpurine DNA-glycosylase and methyl-guanine methyl-transferase in modulating the non-linear dose responses observed in human cells exposed to ethyl methanesulfonate (EMS) and N-methyl-N-nitrosourea, respectively. We also discuss the exposure of binary mixtures, and how combinations of the dissimilar acting agents Benomyl and EMS at their no observed genotoxic effect levels, induce a significant increase in micronuclei.<br>
収録刊行物
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- Genes and Environment
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Genes and Environment 34 (4), 179-185, 2012
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詳細情報 詳細情報について
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- CRID
- 1390282680234628864
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- NII論文ID
- 10031125867
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- NII書誌ID
- AA1212552X
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- ISSN
- 18807062
- 18807046
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- NDL書誌ID
- 024102643
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可