Document Detail

3T3 NIH murine fibroblasts and B78 murine melanoma cells expressing the Escherichia coli N3-methyladenine-DNA glycosylase I do not become resistant to alkylating agents.
MedLine Citation:
PMID:  8118939     Owner:  NLM     Status:  MEDLINE    
The role of alkylation of the N3 position of adenine in the cytotoxicity of alkylating agents in mammalian cells is still undefined. By co-transfecting NIH3T3 murine fibroblast and murine B78 H1 melanoma cells with pSG5tag and pSV2neo, we obtained clones expressing the mRNA of the bacterial tag gene coding for N3-methyladenine-DNA glycosylase I (Gly I), which specifically repairs N3-methyladenine. The levels of Gly I were 400 times higher in NIH3T3 pSG5tag (clone 3.9.4) and 12-33 times higher in B78 H1 tag clones (2A4, 2A6, 2C3 and 2D1) than in the respective control cells. The sensitivity to alkylating agents was evaluated in tag-expressing cells in comparison with pSG5, pSV2neo co-transfected control cells. As regards the cytotoxic activity of methylating agents (N-methylnitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine, dimethylsulfate and temozolomide) and other alkylators with different structure and different interactions with DNA such as CC-1065 and FCE-24517 (minor groove binders known to bind to N3 of adenine), 4-[bis(2-chloroethyl)amino]-L-phenylalanine and cis-diamminedichloroplatinum II, cytotoxicity was the same for tag-expressing and non-expressing cells. These results suggest that the increased expression of N3-methyladenine-DNA glycosylase is not necessarily a crucial mechanism for the resistance of cells to alkylating agents.
L Imperatori; G Damia; P Taverna; E Garattini; L Citti; L Boldrini; M D'Incalci
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Carcinogenesis     Volume:  15     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  1994 Mar 
Date Detail:
Created Date:  1994-04-07     Completed Date:  1994-04-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  533-7     Citation Subset:  IM    
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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MeSH Terms
3T3 Cells / drug effects,  enzymology*
Adenine / analogs & derivatives*
Alkylating Agents / pharmacology
Drug Resistance / genetics
Escherichia coli / enzymology*,  genetics
Gene Expression Regulation, Enzymologic
Genes, Bacterial*
Melanoma / drug therapy,  enzymology*,  genetics
N-Glycosyl Hydrolases / genetics,  metabolism*
RNA, Messenger / metabolism
Tumor Cells, Cultured
Reg. No./Substance:
0/Alkylating Agents; 0/RNA, Messenger; 73-24-5/Adenine; EC 3.2.2.-/N-Glycosyl Hydrolases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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