Removal of excess nuclear protein from cells heated in different physiological states

The relationship between heat-induced cell kill and alterations in nuclear protein content was investigated by heating quiescent 66 mouse mammary adenocarcinoma cells in three different physiological states: (1) quiescent, nutrient deprived cells (Q); (2) Q cells placed in fresh medium 2 h prior to heating (QM); and (3) Q cells made thermotolerant by a previous heat treatment (QTT). Although cell survival varied by a factor of 80, the increase in nuclear protein after a 30 min exposure to 45°C was similar in Q, QM and QTT cells. Removal of the excess nuclear protein from cells in the three physiological states differed both in the percentage of the population that could remove the protein and the rate at which the protein was removed. While all of the QM and QTT cells removed the excess nuclear protein, approximately 30% of the Q cells did not remove the excess nuclear protein, and continued to accumulate protein over the 48 h after the heat treatment. The time for complete removal of the excess protein (Q, 32 h: QM, 18 h: QTT, 8 h) was directly correlated with cell survival. Therefore, these data support the hypothesis that the removal of excess nuclear protein after heat treatment is related to and, perhaps, a determinant of, cell survival.