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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The effect of a novel taurine nitrosourea, 1-(2-chloroethyl)-3-[2-(dimethylaminosulfonyl)ethyl]-1-nitrosour ea (TCNU) on cytotoxicity, DNA crosslinking and glutathione reductase in lung carcinoma cell lines.

A novel nitrosourea, 1-(2-chloroethyl)-3-[2-(dimethylaminosulfonyl)ethyl]-1-nitrosourea (TCNU) has been investigated with respect to cytotoxic mechanisms in rat and human cell lines which either possess (Mer+) or lack (Mer-) 0(6)-alkylguanine transferase activity. TCNU produced significantly greater cytotoxicity in the Mer- cells (Walker 256 rat breast carcinoma resistant to nitrogen mustards; human lung carcinoma A427) than in the Mer+ cells (Walker 256 wild-type; human lung carcinoma A594). This correlated with results generated by alkaline elution studies which showed that TCNU caused DNA interstrand crosslinks in A427 but not in A549 cells. Inhibition of glutathione reductase activity by TCNU demonstrated that in carbamoylating activity the drug was intermediate between chlorozotocin and 1,(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in both A427 and A549 cells. These data suggest that the presence of taurine in the drug structure does little to alter the cytotoxicity or the alkylating or carbamoylating properties of TCNU, and that any clinical advantages with TCNU will be the consequence of other factors.[1]


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