Density dependent regulation of growth in L‐cell suspension cultures. IV. Adaptive and nonadaptive respiratory decline

Respiration as an index of oxidative energy production was investigated in a L‐cell suspension culture system previously shown to exhibit density‐dependent inhibition of growth. It was found that as cultures progressed from exponential growth to high density nongrowing populations (6 −10 × 10 6 cells/ml) over a 2‐week period, the respiratory rate determined from the total amount of oxygen consumed during the daily medium renewal cycle, declined from 5.4 to 1.8 fmoles O 2 /cell/min. There are two components in this decrement. The first consists of a daily recurrent decline of oxygen uptake resulting from decreased availability of medium oxygen and glutamine and is readily reversed by medium supplementation. The second component which is refractory to medium supplementation and accounts for approximately 50% of the total respiratory decline, is considered to indicate an adaptive change of the respiratory capacity of the cells. This change is reversed during the lag period which precedes resumption of exponential growth upon subculture to low cell densities. The significance of these results is discussed in relation to recent reports indicating a marked depression of respiratory activity in nongrowing dense attached cultures as well.