Cellular effects of the anticancer drugs adriamycin and vincristine
Cellular effects of the anticancer drugs adriamycin and vincristine
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.
University of Southampton
1983
Walling, Jacqueline Mary
(1983)
Cellular effects of the anticancer drugs adriamycin and vincristine.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
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.
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Published date: 1983
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Local EPrints ID: 460115
URI: http://eprints.soton.ac.uk/id/eprint/460115
PURE UUID: 2949968c-82cc-4ffd-a50f-bba474d4ed9d
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Date deposited: 04 Jul 2022 17:55
Last modified: 04 Jul 2022 17:55
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Author:
Jacqueline Mary Walling
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