Journal article
Modulation of target enzyme associated with the action of antifolates
Advances in enzyme regulation, Vol.34(C), pp.57-70
1994
DOI: 10.1016/0065-2571(94)90008-6
PMID: 7942285
Abstract
The cytotoxicity and molecular effects of antifolate thymidylate synthase inhibitor, ICI-D1694, against human ileocecal carcinoma, were evaluated. The drug concentration for 50% inhibition of cell growth by ICI-D1694 is 73 n
m and 3 n
m following 2 hr and 72 hr exposure, respectively. The drug induces high level of DNA single strand breaks in a time dependent manner, but subsequent to maximum inhibition of thymidylate synthase. Drug effects can be reversed by thymidine and leucovorin at
> 1 μ
m
concentrations. Leucovorin action is primarily at the cell membrane level, competing with the transport and activation of ICI-D1694. Thymidine, however, exerts its competitive effect primarily at the level of thymidylate synthase.
Details
- Title: Subtitle
- Modulation of target enzyme associated with the action of antifolates
- Creators
- Youcef M. Rustum - Roswell Park Cancer InstituteShousong Cao - Roswell Park Cancer InstituteMing-Biao Yin - Roswell Park Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Advances in enzyme regulation, Vol.34(C), pp.57-70
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/0065-2571(94)90008-6
- PMID
- 7942285
- ISSN
- 0065-2571
- eISSN
- 1873-2437
- Language
- English
- Date published
- 1994
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359686802771
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