Altered growth control by natural growth inhibitors in the mutant HD33 substrain of the Ehrlich-Lettré ascites mammary carcinoma.

The mutant substrain HD33 of the Ehrlich-Lettré ascites mammary carcinoma (EAC) was found to be altered in its ability to respond to and to produce natural growth inhibitors. Cells of this substrain did not respond to (1) a highly purified growth inhibitor from bovine mammary gland, inhibiting the proliferation of two strains of the original EAC already at concentrations of 0.5-2.0 ng/ml, (2) inhibitory activities found in the ascites fluid of these sensitive strains and partially purified. However, from the ascites fluid of the mutant substrain an inhibitory activity was partially purified, which was inhibitory towards this substrain. It also inhibited the cells from an original strain, although less effectively. This new inhibitory activity is similar in its properties to that of the others investigated in that its mol. wt is between 10,000 and 50,000 D, it is heat labile and its activity can be overcome by insulin, epidermal growth factor and 2'-deoxycytidine, the dose-response curve levels off at 35-45% inhibition. The results demonstrate that the regulation of cell proliferation by endogenous (autocrine) inhibitors can be altered by mutagen treatment.