BB-10010, an analog of macrophage inflammatory protein-1alpha, protects murine small intestine against radiation.

Irradiation of the small intestine can result in depletion of the epithelial stem cell compartment and is often the dose-limiting factor for radiotherapeutic treatment of tumors in the abdominal and pelvic region. Since mitotic cells are most sensitive to radiation, significant radioprotection can be achieved by reducing the number of cells in mitosis at the time of irradiation. We have previously shown that administration of macrophage inflammatory protein (MIP) -1alpha induces a transient 50% reduction in the number of mitotic cells in small intestinal crypts, including the stem cell region, and therefore, MIP-1alpha pretreatment before radiation exposure could result in a substantial reduction of the side effects associated with radiotherapy. Groups of adult mice were exposed to different doses of radiation (6, 8, 10, or 12 Gy), with or without prior administration of 200 microg BB-10010/kg 3 hr before irradiation and radiation damage was assessed by means of the microcolony survival assay. MIP-1alpha pretreatment resulted in significantly increased numbers of surviving crypts (10%) when compared to untreated irradiated animals. The observed radioprotective effects of MIP-1alpha in the small intestine should translate into reduced side effects in a clinically relevant radiotherapy context and could allow larger doses of radiation to be delivered to patients with tumors in the abdominal or pelvic region.