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Overexpression of human DNA repair protein N-methylpurine-DNA glycosylase results in the increased removal of N-methylpurines in DNA without a concomitant increase in resistance to alkylating agents in Chinese hamster ovary cells

Overexpression of human DNA repair protein N-methylpurine-DNA glycosylase results in the... N-Alkylpurines induced in DNA by simple monofunctional alkylating agents are known to be cytotoxic and possibly indirectly mutagenic. These adducts are removed by the ubiquitous N-methylpurine-DNA glycosylase (MPG) in a multistep repair pathway. Chinese hamster ovary (CHO) cell clones expressing 2- to 16-fold enhanced levels of MPG activity were isolated from cells stably transfected with human MPG cDNA expression plasmids. The in vivo removal of 3-methyladenine and 7-methylguanine from some of these lines was analyzed and was observed to reflect their MPG levels. These cell lines did not develop increased resistance, as compared to the control, in regards to cytotoxic, mutagenic and sister chromatid exchange inducing effects of the alkylating agents that induce 3-alkyladenine and 7-alkylguanine as the major alkyl adducts in DNA. These results suggest that the MPG activity is not limiting in the multi-step repair pathway of N-alkylpurines in CHO cells. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Carcinogenesis Oxford University Press

Overexpression of human DNA repair protein N-methylpurine-DNA glycosylase results in the increased removal of N-methylpurines in DNA without a concomitant increase in resistance to alkylating agents in Chinese hamster ovary cells

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Publisher
Oxford University Press
Copyright
© Oxford University Press
ISSN
0143-3334
eISSN
1460-2180
DOI
10.1093/carcin/13.11.1989
Publisher site
See Article on Publisher Site

Abstract

N-Alkylpurines induced in DNA by simple monofunctional alkylating agents are known to be cytotoxic and possibly indirectly mutagenic. These adducts are removed by the ubiquitous N-methylpurine-DNA glycosylase (MPG) in a multistep repair pathway. Chinese hamster ovary (CHO) cell clones expressing 2- to 16-fold enhanced levels of MPG activity were isolated from cells stably transfected with human MPG cDNA expression plasmids. The in vivo removal of 3-methyladenine and 7-methylguanine from some of these lines was analyzed and was observed to reflect their MPG levels. These cell lines did not develop increased resistance, as compared to the control, in regards to cytotoxic, mutagenic and sister chromatid exchange inducing effects of the alkylating agents that induce 3-alkyladenine and 7-alkylguanine as the major alkyl adducts in DNA. These results suggest that the MPG activity is not limiting in the multi-step repair pathway of N-alkylpurines in CHO cells.

Journal

Carcinogenesis – Oxford University Press

Published: Nov 1, 1992

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