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

Department of Radiology, Division of Radiotherapy, University of Maryland School of Medicine, Baltimore 21201 [J. E. P.] and Departments of Pathology, Johns Hopkins University School of Medicine, Baltimore 21205, and Baltimore City Hospitals, Baltimore, Maryland 21224 [D. B.]

The subcellular distribution of various lysosomal hydrolases and mitochondrial cytochrome c oxidase of mammary carcinomas of C3H mice was studied by means of differential centrifugation and zonal ultracentrifugation 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, time- and 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 mitochondrial 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 biochemical 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.

¹ Supported by USPHS Research Grants CA06518 and CA 08518 from the National Cancer Institute and partially supported by American Cancer Society Institutional Grant IN-23-L.

² Present address: Departments of Biochemistry and Therapeutic Radiology, Tufts University School of Medicine, Boston, Mass.

Received 5/12/70. Accepted 11/17/70.