Abstract
This thesis reports the results of studies into the effects of various growth inhibitory metabolites upon a murine hybridoma cell line. The cells were examined in vitro and subjected to many different such metabolic stresses as the effects of waste products of normal metabolism such as lactic acid and ammonia. Data presented suggests that these factors alone are not soley responsible for the inhibitory effects observed upon cell growth at high cell concentrations. A cytotoxic effect was also produced by the hybridomas on addition of a dilution of medium that had been exposed to a high concentration of the test cell line for a short period of time. The effect was determined to be not due to the concentrations of lactic acid and ammonium ions present, and further analyses of this medium were carried out. Separation was effected by means of F.P.L.C. and cytotoxic materials were identified in several peaks derived from the medium. The material was identified as being proteinaceous, and proved cytotoxic at high dilutions. The presence of such proteins may be of importance in high cell concentration bioreactors, as they may be retained and so accumulate and prevent optimisation of culture conditions and hence product formation. Further studies may prevent such products being formed or alleviate their effect upon cellular growth.