Analysis of Methylglyoxal Toxicity in Hybridoma Cell Culture

Abstract

Methylglyoxal (MG) is a toxic compound which is produced in cells as a byproduct of glycolysis. Recently, the compound has been suggested as a damaging agent in batch cultures of production cell lines. In the current study, the toxicity of MG is quantified in hybridoma cell lines and compared to that of another commonly cited toxin, lactate. The median inhibitory concentration of viable cell density in batch hybridoma cultures during a 24 hour experiment was found to be 0.483 +/- 0.016 mM for MG, as compared to 77.6 +/- 5.3 mM for lactate. Methylglyoxal induced cell death rapidly; major reductions in viability were observed after approximately five hours of exposure. Methylglyoxal was also shown to strongly stimulate apoptosis; the toxin induced 81 +/- 7% apoptotic cell death versus 37 +/- 11% for lactate. Results for the effects of both toxins on hybridoma cells are discussed in the context of levels encountered during batch cultures. A mathematical model for intracellular MG levels is also presented here.