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Title: Cellular effects of the anticancer drugs adriamycin and vincristine
Author: Walling, Jacqueline Mary
ISNI:       0000 0001 3557 5216
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 1983
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This study had 3 objectives. (1) to determine the nature of adriamycin cytotoxicity towards A. proteus and CHO cells and to assess the relative importance of cytoplasmic and nuclear damage (2) to examine whether cell synchronisation is induced by vincristine and if so whether it is of primary importance in the response of cells exposed to both adriamycin and vincristine, and (3) to examine the nature of cellular interaction between both cytotoxics. Adriamycin was found to have a multiplicity of subcellular targets including the cell membrane, cytoplasmic organelles and nuclear structures. The importance of any one of these targets may depend on both the conditions found within the cell and the oanposition of fluids bathing the cell. The cell membrane and or cytoplasm appears to be the most important determinant of the cytotoxicity of adriamycin towards A. proteus, whereas damage to the nucleus may be more important in CHO cells. Membranal damage induced by adriamycin in CHO cells was important however. As expected, vincristine was found to block CHO cells in metaphase thereby raising the mitotic index. It did not induce SCE and the pattern of chromosomal aberrations induced by vincristine was consistent with interference with spindle dynamics rather than direct chromosomal interaction. Cells exposed to high concentrations of vincristine were found not to reenter the cell cycle after blocking. The primary response to log phase CHO cultures exposed to combinations of adriamycin and vincristine was determined by length of exposure to adriamycin. This was true in terms of cytotoxicity, ultrastructural damage, mitotic index and chromosomal aberrations. Plateau phase cultures were less dependent on drug scheduling for their response. These findings are discussed in terms of their implications for therapy.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Pharmacology & pharmacy & pharmaceutical chemistry