Camptothecin is a plant alkaloid with strong antitumor activity in experimental animals. Its cellular target has recently been identified to be DNA topoisomerase I, an important nuclear enzyme involved in a number of DNA processes such as DNA replication and RNA transcription. A number of camptothecin derivatives (e.g. 9-amino-camptothecin and 10, 11- methylenedioxy-camptothecin) have shown strong antitumor activity against human colon xenografts in nude mice. Because of the potential importance of camptothecin in cancer chemotherapy, we propose to study the mechanism of action of camptothecin and its analogs using human colon tumors as a model system. This program has four specific aims; (1) we will provide a panel of in vitro assays for selecting the most potent camptothecin analogs for in vivo testing. (2) We will study the possible altered regulation of toposomerase I in colon tumors. (3) We will investigate the interaction between replication complex and camptothecin-induced DNA """"""""damage"""""""". (4) We will study the molecular mechanism underlying camptothecin resistance.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA050529-03
Application #
3773502
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
New York University
Department
Type
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
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