Journal article
Cellular heterogeneity in DNA damage and growth inhibition induced by ICI D1694, thymidylate synthase inhibitor, using single cell assays
Biochemical pharmacology, Vol.48(5), pp.997-1002
1994
DOI: 10.1016/0006-2952(94)90370-0
PMID: 8093112
Abstract
Heterogeneity in the response of the HCT-8 (human ileocecal adenocarcinoma) tumor cell line to a new thymidylate synthase inhibitor, ICI D1694, was investigated in terms of induction of DNA single-strand breaks and cytotoxicity, applying the single cell alkaline gel (SCG) electrophoresis assay and the individual colony formation assay (iCFA), respectively. ICI D1694 induced maximal total DNA single-strand breaks 24 hr after a 2-hr drug exposure with incomplete repair by 72 hr. The level of DNA damage was concentration dependent and paralleled cellular growth inhibition
in vitro. The proportion of cells with DNA damage and the extent of DNA single-strand breaks increased with drug concentration. At 1 μM ICI D1694 (
ic
95), a significant level of DNA damage was detected in 58% of the cells; however, 25% of the cells had little or no damage. Using the iCFA system, it was observed that with 1 μM ICI D1694, only 2.6% of the seeded cells maintained a colony growth rate similar to that of the control colonies, and 22% of the cells were growing significantly more slowly. In conclusion, the SCG assay and the iCFA identified subpopulations of cells that were unaffected by ICI D1694. Although these cells represented only a small proportion of the total cell population, this phenomenon of heterogeneity in response to ICI D1694 might limit its therapeutic efficacy.
Details
- Title: Subtitle
- Cellular heterogeneity in DNA damage and growth inhibition induced by ICI D1694, thymidylate synthase inhibitor, using single cell assays
- Creators
- Christoph Schöber - Roswell Park Cancer InstituteJohn F. Gibbs - Roswell Park Cancer InstituteMing-Biao Yin - Roswell Park Cancer InstituteHarry K. Slocum - Roswell Park Cancer InstituteYoucef M. Rustum - Roswell Park Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Biochemical pharmacology, Vol.48(5), pp.997-1002
- Publisher
- Elsevier Inc
- DOI
- 10.1016/0006-2952(94)90370-0
- PMID
- 8093112
- ISSN
- 0006-2952
- eISSN
- 1873-2968
- Language
- English
- Date published
- 1994
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359903002771
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