We propose to contribute to cancer therapy by improving cytokinetic methods and applying them to understand the growth kinetics of cancer cells from man and experimental animals in the context of cancer therapy with cell cycle specific agents. In particular, we are continuing development of: 1) our procedure for simultaneously measuring the extent of incorporation of nonradioactive DNA precursor(s) like bromodeoxyuridine, and total cellular DNA content in a rapid, quantitative and simple method for cytokinetic analysis of cell populations in the midst of therapy; 2) monoclonal antibodies against iododeoxyuridine incorporated into DNA to provide additional markers of DNA synthesis, against ara-C incorporated into DNA for flow cytometric detection of ara-C sterilized cells and against ara-Cmetabolites for improved quantification of intracellular levels of these metabolites, and 3) analytical cytokinetic procedures applicable to therapeutically perturbed populations. We will apply our battery of cytokinetic procedures to analysis of the KHT tumor in C3H mice and the slow growing human NHIK 1922 tumor in nude mice before and during multidose therapy with cytosine arabinoside (ara-C). We will: 1) measure the metabolic and cytokinetic phenomena associated with ara-C to develop a quantitative basis for adjusting cytokinetic-based schedules to compensate for changes in dose level. 2) Characterize the cytokinetic properties of tumors throughout a multidose course of ara-C to estimate how well they can be extrapolated to immeasurably small tumor residuals and 3) combine on data on mid-therapy cyktokinetic properties of the NHIK 1922 tumor with similar data on the intestinal and bone marrow cells in the host mouse to determine if therapeutic advantages based on pretreatment cytokinetic differences between tumor and normal tissues remain during therapy and can be effectively exploited.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA014533-13
Application #
3163943
Study Section
Radiation Study Section (RAD)
Project Start
1977-09-01
Project End
1986-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
13
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Lawrence Livermore National Laboratory
Department
Type
Organized Research Units
DUNS #
827171463
City
Livermore
State
CA
Country
United States
Zip Code
94550
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Stanker, L H; Branscomb, E; Vanderlaan, M et al. (1986) Monoclonal antibodies recognizing single amino acid substitutions in hemoglobin. J Immunol 136:4174-80
Vanderlaan, M; Watkins, B; Thomas, C et al. (1986) Improved high-affinity monoclonal antibody to iododeoxyuridine. Cytometry 7:499-507
Rice, G; Laszlo, A; Li, G et al. (1986) Heat shock proteins within the mammalian cell cycle: relationship to thermal sensitivity, thermal tolerance, and cell cycle progression. J Cell Physiol 126:291-7
Gray, J W; Dolbeare, F; Pallavicini, M G et al. (1986) Cell cycle analysis using flow cytometry. Int J Radiat Biol Relat Stud Phys Chem Med 49:237-55
Kurki, P; Vanderlaan, M; Dolbeare, F et al. (1986) Expression of proliferating cell nuclear antigen (PCNA)/cyclin during the cell cycle. Exp Cell Res 166:209-19
Rice, G C; Gray, J W; Dewey, W C (1985) FACS analysis of a hyperthermia-induced alteration in Hoechst 33342 permeability and direct measurement of its relationship to cell survival. J Cell Physiol 122:387-96
Xue, S B; Paiiavicini, M G; Gray, J W (1985) Double label radioactivity per cell (RC) analysis in vivo: rapid cytokinetic analysis of the KHT sarcoma. Shi Yan Sheng Wu Xue Bao 18:215-24
Pinkel, D; Thompson, L H; Gray, J W et al. (1985) Measurement of sister chromatid exchanges at very low bromodeoxyuridine substitution levels using a monoclonal antibody in Chinese hamster ovary cells. Cancer Res 45:5795-8
Vanderlaan, M; Thomas, C B (1985) Characterization of monoclonal antibodies to bromodeoxyuridine. Cytometry 6:501-5

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