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An investigation into the effects of inhibitors of DNA biosynthesis on monoclonal antibody production in hybridoma cell cultures.

Modha, Kishor. (1990) An investigation into the effects of inhibitors of DNA biosynthesis on monoclonal antibody production in hybridoma cell cultures. Doctoral thesis, University of Surrey (United Kingdom)..

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The results of this investigation demonstrated that antibody production in MAK 33 cells was not growth dependent suggesting that antibody synthesis could be maintained in the absence of cell division. The inhibition of cell growth with specific inhibitors of DNA synthesis enhanced the cell specific antibody production rate (CSAPR). Studies on the metabolism of MAK 33 cells under growth inhibited conditions showed that the rise in CSAPR was correlated with the rise in intracellular ATP concentration and the increase in the uptake rates of glucose and glutamine. These results suggested that one of the key factors initiating the rise in CSAPR was the increase in the availability of ATP for antibody synthesis. The rise in intracellular ATP concentration was proposed to be a consequence of the following changes in cell metabolism; 1. Increase in anaerobic glycolysis demonstrated by a concurrent rise in glucose consumption and lactate production. 2. The salvage of energy normally utilised in the processes pertaining to cell division (DNA synthesis and mitosis). Also as part of this investigation a screening assay was developed which could identify compounds with the potential to arrest cell division via the inhibition of DNA synthesis without impairing antibody synthesis. Upon the application of some of the compounds identified by the screening assay to 0.5 litre stirrer cultures, it was discovered that both CSAPR and antibody yield could be enhanced if growth was arrested in mid-exponential phase. These results demonstrated that antibody yield of a batch culture was a function of both viable cell number and CSAPR. Both parameters should be considered with equal importance when designing production strategies intended to improve the antibody yield.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors :
Modha, Kishor.
Date : 1990
Contributors :
Depositing User : EPrints Services
Date Deposited : 09 Nov 2017 12:13
Last Modified : 15 Mar 2018 23:04

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