Effect of X-irradiation on the Functional Status of Lysosomal Enzymes of Mouse Mammary Gland Carcinomas1

The subcellular distribution of various lysosomal hydrolases and mitochondria! cytochrome c oxidase of mammary carcinomas of C3H mice was studied by means of differential centrifugation and zonal ultracentriftigation and in electron histochemical preparations. Tumors that received a single local dose of 500, 1000, or 7000 rad showed an increase in the specific activities of acid hydrolases in the whole homogenates. Under the same conditions, timeand dose-dependent increases in the proportion of absolute unsedimentable activities were observed. These changes appeared not earlier than 6 hr after doses of 7000 rad. Whole homogenates from animals receiving a combined treatment of X-irradiation plus vitamin A showed higher levels of specific acid hydrolases than those from mice treated with radiation alone, and homogenates from mice given X-irradiation plus cortisone showed lower levels of acid-hydrolytic activity than those from irradiated animals. A peak of fast-moving acid hydrolases that precedes the mitochondria! fraction in the high-resolution zonal ultracentrifugation techniques appears clearly enlarged in tumors treated with 1000 rad. These samples also showed a decrease of mitochondrial cytochrome c oxidase. The bio chemical and electron histochemical changes observed indicate an involvement of the lysosome system in regressing mammary carcinomas. The fact that the course of biochemical events in the irradiated tumors is modified by lysosome labilizers or stabilizers is also in favor of this hypothesis.