M. Newland et al., AMMONIA INHIBITION HYBRIDOMAS PROPAGATED IN BATCH, FED-BATCH, AND CONTINUOUS-CULTURE, Biotechnology and bioengineering, 43(5), 1994, pp. 434-438
The nature and temporal development of ammonia inhibition were investi
gated in batch, fed-batch, and continuous cultures. Significant inhibi
tion was observed when cells were inoculated in serum-containing or ch
emically defined medium containing more than 2 mM of ammonia. In contr
ast, no inhibition was observed at greater than 10 mM when the ammonia
concentration was gradually increased over the span of a batch cultur
e by feeding ammonium chloride. Strong growth inhibition was observed
after each of five step changes (2.8 --> 3.7 --> 4.0 --> 4.9 --> 7.7 -
-> 13.5 mM) in continuous culture. Following a period of adaptation at
each higher value, the viable cell density stabilized at a new lower
value. The lowering in viable cell density was caused by an increase i
n specific death rate and a decreased cell yield on glucose, glutamine
, and oxygen. Increased ammonia concentration had little or no effect
on the steady-state specific growth kinetics or specific antibody prod
uctivity. (C) 1994 John Wiley and Sons, Inc.