Journal article 1605 views 284 downloads
Investigating Mechanisms for Non-linear Genotoxic Responses, and Analysing Their Effects in Binary Combination
George Johnson 
,
Zoulikha M Zair,
Owen Bodger ,
Paul Lewis,
Ben J Rees,
Jatin R Verma,
Adam D Thomas,
Shareen H Doak,
Gareth Jenkins
,
Zoulikha M Zair,
Owen Bodger ,
Paul Lewis,
Ben J Rees,
Jatin R Verma,
Adam D Thomas,
Shareen H Doak,
Gareth Jenkins
Genes and Environment, Volume: 34, Issue: 4, Pages: 179 - 185
Swansea University Authors:
George Johnson , Owen Bodger , Paul Lewis, Gareth Jenkins
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DOI (Published version): 10.3123/jemsge.34.179
Abstract
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 fogenotoxic tolerance' at low doses...
| Published in: | Genes and Environment |
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| ISSN: | 1880-7046 1880-7062 |
| Published: |
2012
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| Online Access: |
Check full text
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa13400 |
| Abstract: |
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 fogenotoxic 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. |
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| Item Description: |
Special issue paper: https://www.jstage.jst.go.jp/browse/jemsge/34/4/_contents |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Issue: |
4 |
| Start Page: |
179 |
| End Page: |
185 |