Formation and repair of 1,3-bis-(2-chloroethyl)-1-nitrosourea and cisplatin induced total genomic DNA interstrand crosslinks in human glioma cells.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ali-Osman, F; Rairkar, A; Young, P

Published Date

  • January 1995

Published In

Volume / Issue

  • 14 / 4

Start / End Page

  • 231 - 241

PubMed ID

  • 7767897

Pubmed Central ID

  • 7767897

International Standard Serial Number (ISSN)

  • 0305-7232

Language

  • eng