Lysosomes in mice mammary tumors treated with cyclophosphamide:Distribution related to course of disease

Abstract

Transplantable carcinomas of mouse mammary gland were treated with cyclophosphamide at various dose levels ranging from 50 to 300 mg/kg body weight. The degree and the length of the period of tumor growth inhibition increased with the dose. Increased activity of the lysosomal enzyme, acid phosphatase, was observed in the tumor cells of treated mice, especially at the dose levels of cyclophosphamide that inhibited tumor growth (200 to 300 mg/kg). Lysosomal acid phosphatase activity remained present during the entire period of growth inhibition but decreased at the time when tumor growth was resumed and disappeared almost completely when the growth rate approximated that of the untreated controls. Combined treatment with the cytotoxic agent and a lysosomal labilizer, vitamin A, increased both the inhibitory effect of cyclophosphamide and the acid phosphatase activity in the tumor cells. In the electron microscopic preparations, the tumor cells of treated mice showed areas of focal degradation and widespread ultrastructural alterations which frequently were associated with lysosomes.