Heterogeneity in induced heat resistance and its relation to synthesis of stress proteins in rat tumor cell clones.

Tumor cell clones isolated from a rat 13762NF mammary adenocarcinoma and its spontaneous metastases were heterogeneous in their survival responses to continuous 42 degrees heating. Clones MTLn3 and MTF7 had similar initial survival responses; they were significantly less sensitive than clone MTC. Following the first decrease in survival, different magnitudes of induced thermal resistance were observed. When ratios of the first and resistant slopes of survival curves were compared (the thermotolerance ratio), the order of induced thermal resistance was MTLn3 greater than MTF7 greater than MTC. These clones were compared for the rates of synthesis of heat stress proteins (HSP). The same four major HSP at Mr 112,000, 90,000, 70,000, and 22,000 were induced or enhanced in all 3 clones. The rates of synthesis of these HSP were analyzed through a unique system of computer-assisted video densitometry and digitization. When all 4 HSP were analyzed as a group, the rates were significantly different (p less than 0.017), and the rank order of rates of synthesis was significant with MTLn3 greater than MTF7 greater than MTC. Induction kinetics of the individual HSP were different. Individually, the HSP at Mr 112,000, 90,000, and 22,000 were synthesized at significantly different rates between clones (p less than 0.001) but the Mr 70,000 HSP was not. Absolute total protein synthesis was highest for clone MTLn3, and MTF7 was higher than MTC but only marginally. Although absolute accumulations of these HSP could not be directly compared between these clones, the higher rates of HSP synthesis in these tumor cell clones correlated with more thermal resistance. These data support the working hypothesis that one or more of these HSP have a direct role in the mechanism(s) for inducing thermal resistance in rat tumor cells, but other factors such as total protein synthesis could modify the complex bio-chemical and phenotypic pathways involved in induced HSP and thermal resistance.