Quantitation of resistance of leukemic cells to cytosine arabinoside from BrdUrd/DNA bivariate histograms

✍ Scribed by F. Lacombe; F. Belloc; P. Dumain; M. Puntous; F. Lopez; P. Bernard; M. R. Boisseau; J. Reiffers

• Book ID: 102818226
• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 783 KB
• Volume: 13
• Category: Article
• ISSN: 0196-4763
• DOI: 10.1002/cyto.990130709

✦ Synopsis

The cytotoxicity of ara-C derives from an inhibition of DNA synthesis after incorporation of ara-CTP into DNA. The rate of DNA synthesis can be determined from the amount of bromodeoxy-uridine (BrdUrd) incorporated into cells after a short exposure to BrdUrd. We developed a computer program to quantify the inhibition of the rate of DNA synthesis by analysis of the distribution of BrdUrcU DNA. Inhibition was evaluated in ara-Csensitive and resistant cells after incubation with different doses of ara-C. An index of resistance to ara-C (RI) was expressed as the ratio of the amount of BrdUrd incorporated into S phase cells incubated with ara-C to that incorporated in the absence of ara-C. In the ara-C-sensitive and resistant HL60 cells, a linear relationship between RI and log ara-C concentration was observed. Small numbers of slightly resistant cells in mixtures of ara-C-sensitive and resistant cells could be determined using this method, making it suitable for clinical use to test the resistance of leukemic cells t o ara-C.