Radiation-induced apoptosis in peritoneal resident macrophages of C3H mice: selective involvement of superoxide anion, but not other reactive oxygen species.

Remarkably, apoptosis was induced by gamma-ray-irradiation in peritoneal resident macrophages (PRM) of C3H mice, but not other strains of mice. The mechanism of this strain-specific apoptosis induction was studied. Apoptosis in PRM was detected microscopically. Various radical scavengers were examined to identify the critical radicals involved in apoptosis induction. Intracellular peroxide levels were measured with a redox-sensitive dye, 2',7'-dichlorofluorescin diacetate (DCFH). Superoxide dismutase or catalase was introduced into the cells using commercially available Hemagglutinating Virus of Japan (HVJ) envelope vector kit. The enzyme activity of superoxide dismutase was also measured. Radiation-induced apoptosis in C3H mouse PRM was significantly suppressed by treatment with a pharmacological scavenger of superoxide anion, Tiron, but not with other radical scavengers. Intracellular peroxide levels were not elevated by irradiation at doses high enough to induce apoptosis maximally. Radiation-induced apoptosis in C3H mouse PRM was markedly suppressed by superoxide dismutase introduced into the cells using the HVJ envelope vector, but not catalase. The enzyme activity of superoxide dismutase in C3H mouse PRM was comparable with that in B6 mouse PRM. It was concluded that superoxide played the major role in radiation-induced apoptosis in the C3H mouse PRM and that cellular responses downstream or unrelated to superoxide might be responsible for the strain difference in radiation-induced apoptosis of mouse PRM.