Studies on the mechanisms of tumorigenesis induced by polyetherurethane in rats: production of superoxide, tumor necrosis factor, and interleukin 1 from macrophages cultured on different polyetherurethanes.

Interaction of macrophages (Mos) with polyetherurethane (PEU) was investigated to clarify the role of the Mos in the early stage of tumorigenesis of PEUs. As for the inflammatory cytokines produced from Mos, the amount of tumor necrosis factor (TNF) produced on three PEUs (PU-4, 6, and 8) was similar, but less than that on a control glass dish. Interleukin 1 (IL-1) production levels on the PEUs, especially on PU-6, also decreased in comparison with the glass dish. Superoxide (O(2)(-)) release from Mos on the PEUs was similar or more than that on the glass dishes within 24 h incubation. In particular, the O(2)(-) release on PU-6, possessing the lowest tumorigenic potential in vivo, reached the highest level among the PEUs tested. To clarify the causes that enhanced O(2)(-) release from Mos, the methanol extracts of the three PEUs and chemicals that constitute the PEUs were tested. The extracts and 1,4-butanediol did not show an effect on O(2)(-) release. However, 4, 4'-di(ethoxycarboamide) diphenylmethane, a model hard segment of PEU, was remarkably enhanced, whereas poly(tetramethyleneoxide), a soft segment of PEU, reduced the O(2)(-) release in a dose-dependent manner. From these results, although it is still unclear what affects different types of O(2)(-) production, lower tumorigenic potentials of PU-6 may be caused by O(2)(-) release from Mos, which play an important role in the tumoricidal process. Further, the low IL-1 production on PU-6 suggests that PU-6 suppresses inflammatory responses other than O(2)(-) production in vivo, resulting in lower tumorigenic potentials. On the other hand, TNF production was almost similar when Mos were cultured on three PEUs, suggesting TNF did not play a role in the different tumorigenic potentials of PEUs.