Expression in mammalian cells of the Escherichia coli O6 alkylguanine-DNA-alkyltransferase gene ogt reduces the toxicity of alkylnitrosoureas.

2.50
Hdl Handle:
http://hdl.handle.net/10541/100212
Title:
Expression in mammalian cells of the Escherichia coli O6 alkylguanine-DNA-alkyltransferase gene ogt reduces the toxicity of alkylnitrosoureas.
Authors:
Harris, L C; Margison, Geoffrey P
Abstract:
V79 Chinese hamster cells expressing either the O6-alkylguanine-DNA-alkyltransferase (ATase) encoded by the E. coli ogt gene or a truncated version of the E. coli ada gene have been exposed to various alkylnitrosoureas to investigate the contribution of ATase repairable lesions to the toxicity of these compounds. Both ATases are able to repair O6-alkylguanine (O6-AlkG) and O4-alkylthymine (O4-AlkT) but the ogt ATase is more efficient in the repair of O4-methylthymine (O4-MeT) and higher alkyl derivatives of O6-AlkG than is the ada ATase. Expression of the ogt ATase provided greater protection against the toxic effects of the alkylating agents then the ada ATase particularly with N-ethyl-N-nitrosourea (ENU) and N-butyl-N-nitrosourea (BNU) to which the ada ATase expressing cells were as sensitive as parent vector transfected cells. Although ogt was expressed at slightly higher levels than the truncated ada in the transfected cells, this could not account for the differential protection observed. For-N-methyl-N-nitrosourea (MNU) the increased protection in ogt-transfected cells is consistent with O4-MeT acting as a toxic lesion. For the longer chain alkylating agents and chloroethylating agents, the protection afforded by the ogt protein may be a consequence of the more efficient repair of O6-AlkG, O4-AlkT or both of these lesions in comparison with the ada-encoded ATase.
Affiliation:
CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.
Citation:
Expression in mammalian cells of the Escherichia coli O6 alkylguanine-DNA-alkyltransferase gene ogt reduces the toxicity of alkylnitrosoureas. 1993, 67 (6):1196-202 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
Jun-1993
URI:
http://hdl.handle.net/10541/100212
PubMed ID:
8512805
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHarris, L Cen
dc.contributor.authorMargison, Geoffrey Pen
dc.date.accessioned2010-06-03T14:34:34Z-
dc.date.available2010-06-03T14:34:34Z-
dc.date.issued1993-06-
dc.identifier.citationExpression in mammalian cells of the Escherichia coli O6 alkylguanine-DNA-alkyltransferase gene ogt reduces the toxicity of alkylnitrosoureas. 1993, 67 (6):1196-202 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid8512805-
dc.identifier.urihttp://hdl.handle.net/10541/100212-
dc.description.abstractV79 Chinese hamster cells expressing either the O6-alkylguanine-DNA-alkyltransferase (ATase) encoded by the E. coli ogt gene or a truncated version of the E. coli ada gene have been exposed to various alkylnitrosoureas to investigate the contribution of ATase repairable lesions to the toxicity of these compounds. Both ATases are able to repair O6-alkylguanine (O6-AlkG) and O4-alkylthymine (O4-AlkT) but the ogt ATase is more efficient in the repair of O4-methylthymine (O4-MeT) and higher alkyl derivatives of O6-AlkG than is the ada ATase. Expression of the ogt ATase provided greater protection against the toxic effects of the alkylating agents then the ada ATase particularly with N-ethyl-N-nitrosourea (ENU) and N-butyl-N-nitrosourea (BNU) to which the ada ATase expressing cells were as sensitive as parent vector transfected cells. Although ogt was expressed at slightly higher levels than the truncated ada in the transfected cells, this could not account for the differential protection observed. For-N-methyl-N-nitrosourea (MNU) the increased protection in ogt-transfected cells is consistent with O4-MeT acting as a toxic lesion. For the longer chain alkylating agents and chloroethylating agents, the protection afforded by the ogt protein may be a consequence of the more efficient repair of O6-AlkG, O4-AlkT or both of these lesions in comparison with the ada-encoded ATase.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshBacterial Proteins-
dc.subject.meshBase Sequence-
dc.subject.meshCell Survival-
dc.subject.meshClone Cells-
dc.subject.meshCricetinae-
dc.subject.meshDrug Resistance-
dc.subject.meshEscherichia coli-
dc.subject.meshFibroblasts-
dc.subject.meshGene Expression-
dc.subject.meshGuanine-
dc.subject.meshLung-
dc.subject.meshMethyltransferases-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshMutagenesis, Site-Directed-
dc.subject.meshNitrosourea Compounds-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.subject.meshThymine-
dc.subject.meshTransfection-
dc.titleExpression in mammalian cells of the Escherichia coli O6 alkylguanine-DNA-alkyltransferase gene ogt reduces the toxicity of alkylnitrosoureas.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.en
dc.identifier.journalBritish Journal of Canceren
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