The time course and dose response curve for inhibition of DNA synthesis in mouse spleen and jejunum was determined for aphidicolin glycinate, a water soluble ester of aphidicolin currently undergoing preclinical toxicological evaluation. Studies of the biochemical and pharmacologic effects of tiazofurin were continued. The combination of tiazofurin and 5-FU was synergistic in toxicity to L1210 cells.; tiazofurin enhanced the toxicity of 5-FU in non-tumored mice. These effects may be related to a tiazofurin-induced increase in PRPP pools. Cyclopentenyl cytosine was found to have reproducible antitumor activity against L1210 and P388 leukemia in the mouse. A sharp drop in CTP pools of L1210 cells in vivo was observed after treatment, indicating an effect on CTP synthetase in vivo. The perflurocarbon emulsion fluosol-DA was evaluated for its ability to increase the perfusion of solid tumors in vivo. Blood flow in a s.c. implanted solid Walker 256 tumor and in normal rat tissues was determined by 14C-idooantipyrine and autoradiographic techniques. Fluoso-DA did not increase flow to the whole tumor and the pattern of regional flow within the tumor was not substantially altered; whereas cerbral flow was increased two-fold. A gas chromatographic method was developed using nitrogen-phosphorous detectors to quantify thiotepa and its metabolite, TEPA, in extracts of blood and CSF. This technique was used to study the pharmacokinetics of these two compounds in monkeys and man following i.v. and i.t. administration. A method was developed to quanitfy intracellular thioinosine monophosphate and thioguanosine monophosphate to be used in a clinical study of 6-mercaptopurine. A radioactive photoactive anthracycline analog was used to photaffinity label anthracycline binding proteins in P388 cells sensitive and resistant to anthracyclines, and in rat heart homogenates. Specific polypeptides were isolated which may function as mediators of anthracycline activity.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Treatment (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CM006162-01
Application #
4692084
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Cancer Treatment
Department
Type
DUNS #
City
State
Country
United States
Zip Code