The effect of Msh2 knockdown on toxicity induced by tert-butyl-hydroperoxide, potassium bromate, and hydrogen peroxide in base excision repair proficient and deficient cells

Cooley, N, Elder, RH ORCID: https://orcid.org/0000-0003-4614-175X and Povey, AC 2013, 'The effect of Msh2 knockdown on toxicity induced by tert-butyl-hydroperoxide, potassium bromate, and hydrogen peroxide in base excision repair proficient and deficient cells' , BioMed Research International, 2013 .

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Abstract

The DNA mismatch repair (MMR) and base excision repair (BER) systems are important determinants of cellular toxicity following exposure to agents that cause oxidative DNA damage. To examine the interactions between these different repair systems, we examined whether toxicity, induced by t-BOOH and KBrO3, differs in BER proficient (Mpg (+/+), Nth1 (+/+)) and deficient (Mpg (-/-), Nth1 (-/-)) mouse embryonic fibroblasts (MEFs) following Msh2 knockdown of between 79 and 88% using an shRNA expression vector. Msh2 knockdown in Nth1 (+/+) cells had no effect on t-BOOH and KBrO3 induced toxicity as assessed by an MTT assay; knockdown in Nth1 (-/-) cells resulted in increased resistance to t-BOOH and KBrO3, a result consistent with Nth1 removing oxidised pyrimidines. Msh2 knockdown in Mpg (+/+) cells had no effect on t-BOOH toxicity but increased resistance to KBrO3; in Mpg (-/-) cells, Msh2 knockdown increased cellular sensitivity to KBrO3 but increased resistance to t-BOOH, suggesting a role for Mpg in removing DNA damage induced by these agents. MSH2 dependent and independent pathways then determine cellular toxicity induced by oxidising agents. A complex interaction between MMR and BER repair systems, that is, exposure dependent, also exists to determine cellular toxicity.

Item Type:	Article
Schools:	Schools > School of Environment and Life Sciences > Biomedical Research Centre Schools > School of Environment and Life Sciences
Journal or Publication Title:	BioMed Research International
Publisher:	Hindawi
Refereed:	Yes
ISSN:	2314-6133
Related URLs:	Publication
Funders:	European Chemical Industry Council
Depositing User:	RH Elder
Date Deposited:	02 Jun 2015 17:26
Last Modified:	27 Aug 2021 23:16
URI:	https://usir.salford.ac.uk/id/eprint/34646

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