The investigators of this application have shown that greater than additive enhancement of cell kill occurs when alkylating agents (BCNU or cisplatin) are combined with Br-dUrd in an in vitro glioma cell model. The purpose of this grant application is to determine the reason for this enhanced cell kill and to identify determinants of response. To do this they plan to 1) study the alkylation by BCNU of purified dsDNA that contains Br-dUrd in place of dThd, 2) to elucidate the role of the cell cycle in the enhancement of the cell kill seen in these drug combinations, and 3) to evaluate the extent of variation of this phenomenum among glioma cell lines and to identify determinants of response.
| Mancini, W R; Glaze, E R; Stetson, P L et al. (1999) Sensitization of 1,3-bis(2-chloroethyl)-1-nitrosourea and cisplatin cytotoxicity by 5-bromo-2'-deoxyuridine in human glioma. J Pharmacol Exp Ther 289:1404-9 |
