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 cotransfected 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-diamino-dichloroplatinum 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.
|Autori:||L. IMPERATORI; G. DAMIA; P. TAVERNA; E. GARATTINI; L. CITTI; BOLDRINI L; M. D' INCALCI.|
|Titolo:||3T3 NIH murine fibroblasts and B78 murine melanoma cells expressing the "E. coli" N3-methyladenine-DNA glycosylase I do not become resistant to alkylating agents"|
|Anno del prodotto:||1994|
|Digital Object Identifier (DOI):||10.1093/carcin/15.3.533|
|Appare nelle tipologie:||1.1 Articolo in rivista|