Studies on lysosomes—X: Effects of tumor-promoting agents upon biological and artificial membrane systems

Abstract

Six tumor-promoting compounds (crude croton oil, croton oil resin, phorbol esters, Tween 80, Tween 60 and an extract of tobacco leaves) were tested for their activity on biological and artificial membranes. Each of the agents was capable of releasing aryl sulfatase, β-glucuronidase and acid phosphatase from large-granule fractions of rabbit liver (0.25 M sucrose). Release of enzymes was dependent upon time, temperature and concentration of the tumor-promoting agent. The order of activity upon lysosomes closely followed the order of activity of a given agent as a tumorpromoter (co-carcinogen). Although most of the agents were hemolytic and released malate dehydrogenase from mitochondria, their order of activity on red cells and mitochondria was not directly related to tumor-promoting action. All tumor-promoting agents did not release marker anions from artificial lipid spherules, differing in this property from other membrane-active substances such as steroids or polyene antibiotics. Lysosomes from liver were not disrupted by tumor-initiating agents nor by complete, systemic carcinogens, although “proximate carcinogens” other than N-hydroxy-2-acetylaminofluorene were not tested. The results suggest that tumorpromoting agents disrupt biological membranes in vitro and that their order of action in vivo is paralleled by their effects upon lysosomes.