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  • Title: Formation and repair of 1,3-bis-(2-chloroethyl)-1-nitrosourea and cisplatin induced total genomic DNA interstrand crosslinks in human glioma cells.
    Author: Ali-Osman F, Rairkar A, Young P.
    Journal: Cancer Biochem Biophys; 1995 Jan; 14(4):231-41. PubMed ID: 7767897.
    Abstract:
    The kinetics of formation and repair of total genomic DNA interstrand crosslinks (ISCs) induced by BCNU and cis-DDP were studied in cells of 6 human malignant gliomas and related with their degree of drug resistance. DNA ISCs were formed rapidly (peak 6-12 h) following a 2 h exposure to 50 microM BCNU or 25 uM cis-DDP, and on an equimolar basis higher levels of crosslinking were observed with cis-DDP than with BCNU. Repair of cis-DDP induced crosslinks was characteristically bi-phasic and the rate was significantly higher than that for BCNU induced crosslinks. Overall, a low crosslink index and a high crosslink repair rate correlated with cis-DDP and BCNU resistance. The data demonstrate, conclusively, the ability of human glioma cells to repair cis-DDP and, for the first time, BCNU induced DNA ISCs and that DNA crosslink repair is a significant contributing factor to the resistance of these tumors to the two agents.
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