TY - JOUR AU - Chitwood, Dylan G. AU - Wang, Qinghua AU - Elliott, Kathryn AU - Bullock, Aiyana AU - Jordana, Dwon AU - Li, Zhigang AU - Wu, Cathy AU - Harcum, Sarah W. AU - Saski, Christopher A. PY - 2021 DA - 2021/01/08 TI - Characterization of metabolic responses, genetic variations, and microsatellite instability in ammonia-stressed CHO cells grown in fed-batch cultures JO - BMC Biotechnology SP - 4 VL - 21 IS - 1 AB - As bioprocess intensification has increased over the last 30 years, yields from mammalian cell processes have increased from 10’s of milligrams to over 10’s of grams per liter. Most of these gains in productivity can be attributed to increasing cell densities within bioreactors. As such, strategies have been developed to minimize accumulation of metabolic wastes, such as lactate and ammonia. Unfortunately, neither cell growth nor biopharmaceutical production can occur without some waste metabolite accumulation. Inevitably, metabolic waste accumulation leads to decline and termination of the culture. While it is understood that the accumulation of these unwanted compounds imparts a suboptimal culture environment, little is known about the genotoxic properties of these compounds that may lead to global genome instability. In this study, we examined the effects of high and moderate extracellular ammonia on the physiology and genomic integrity of Chinese hamster ovary (CHO) cells. SN - 1472-6750 UR - https://doi.org/10.1186/s12896-020-00667-2 DO - 10.1186/s12896-020-00667-2 ID - Chitwood2021 ER -