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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

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...

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Published in: Genes and Environment
ISSN: 1880-7046 1880-7062
Published: 2012
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa13400
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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.
Item Description: Special issue paper: https://www.jstage.jst.go.jp/browse/jemsge/34/4/_contents
College: Swansea University Medical School
Issue: 4
Start Page: 179
End Page: 185