Genetic Elements for Chemoprotection Against Cyclophosphamide.
Final rept. 19 Aug 96-18 Aug 98,
ILLINOIS UNIV AT CHICAGO CIRCLE
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Our goal is the identification of genes that affect cellular response to an alkylating agent cyclophosphamide CP modulation of expression of these genes should protect cells from CP-induced cytotoxicity. Identification of genes that increasedecrease cytotoxicity of CP will allow for better regimens of autologous hone marrow transplantation, since genetic modification of the patients hone marrow cells before the first round of chemotherapy will reduce myelosuppression and will thus allow for better dose escalation. We have identified four different genetic elements that dramatically increase cell survival after treatment with in vitro active CP analogue mafosfmide. One of genetic elements shares a high degree of homology with a nuclear protein kinase RING3 another is highly homologous to cytochrome oxidase subunit III the other two elements do not have homology in the most recent releases of GeneBank. Protective effect of these elements is most pronounced when all four of them are present. Our current efforts are directed toward identification of full-length cDNA clones and studies of expression of corresponding genes.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research