Biochemical and growth rate changes induced in cultures of human cells by lysosomotropic agents under a variety of experimental conditions will be investigated in detail. Specific variations to be examined include whether such compounds increase nuclear concentrations of non-histone proteins (NHP) by inhibiting their degradation. Since it is known that NHP play a crucial role in cellular growth control, investigations will also be carried out to determine if the above changes on nuclear NHP correlate with quantitative variations on proliferative rates under standard laboratory conditions. A major objective of this proposal will be to determine if the working hypothesis that increased nuclear levels of NHP are a direct consequence of pharmacological inhibition of lysosomal degradation and whether the latter plays an important and until now unrecognized role in the control of cell growth. The above effects will be quantitatively compared in normal and neoplastic human cells to determine whether the altered growth rate of cells is characterized by lysosomal defects. These investigations aim to support the hypothesis that lysosomes play a role in neoplastic growth control and have potential significance on our understanding of mechanisms involved in carcinogenesis. (E)
