Tumorigenesis by Millipore Filters in Mice: Histology and Ultrastructure of Tissue Reactions as Related to Pore Size2

Abstract

Hydrophilic Millipore filter disks, 2.0 cm in diameter, with 8 different pore sizes ranging from 0.025 to 8.0 µm, were subcutaneously implanted into female CBA/H, CBA/H-T6, or (CBA/H × CBA/BrA)F₁ mice. Sarcomas at implant sites developed after 7–27 months in 25 of 31 animals that had received filters with pore sizes of ≤0.1 µm. Filters with pore sizes of ≥0.22 µm were non-tumorigenic. Histologic and ultrastructural studies were done 1, 3, 5, and 10 months post implantation on specimens composed of implants and surrounding tissue reactions. Nontumorigenic filters induced tissue reactions characterized by a) invasion of filters by macrophages or their cytoplasmic processes and b) presence of phagolysosomes within macrophages as evidence of phagocytic activity. In tissue reactions induced by tumorigenic filters, these criteria were always missing; instead, there was more fibrosis which resulted in thicker collagenous tissue capsules. The results permitted assessment of various etiologic hypotheses relating to a) interruption of cellular contact or communication, and b) smoothness, continuity, or electric charge of foreign-body surfaces.