BB-10010, an analogue of macrophage inflammatory protein-1 alpha, reduces proliferation in murine small-intestinal crypts.
BACKGROUND
The small-intestinal epithelium, a rapidly proliferating tissue, is highly sensitive to cycle-specific agents such as radiation. Macrophage inflammatory protein (MIP)-1 alpha has been shown to reduce cell proliferation in bone marrow, seminiferous epithelium, and skin. The current work investigates the activity of an MIP-1 alpha variant, BB-10010, in the gut.


METHODS
A single dose of either 0.4 microg/kg or 200 microg/kg was administered to mice 2, 4, 6, 8, 10, 12, or 14 h before animal death. Fifteen crypts from the midpoint of the small intestine were dissected from each animal and squashed, and the numbers of vincristine-arrested metaphases was counted for each fifth of the crypts.


RESULTS
A 40%-50% reduction of accumulated metaphases throughout all crypt segments was observed in animals injected with 200 microg/kg of BB-10010 2 h and 4 h before death (P < 0.0001). The animals that received 0.4 microg/kg showed a similar effect at 4 h (P < 0.0001).


CONCLUSIONS
The results provide evidence of a significant reduction in numbers of intestinal cryptal cells passing through mitosis at specific time periods after a single administration of BB-10010. By putting these cells temporarily out of the mitotic phase of the cell cycle this protein might reduce the side effects of radiation therapy to patients undergoing abdominal or pelvic treatments.
Arango
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School of Diagnostic Imaging and Dept. of Human Anatomy, University College Dublin, Ireland.
Ettarh
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RR
Brennan
P C
PC
D000818:Animals; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D004305:Dose-Response Relationship, Drug; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects*; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects*; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D008297:Male; D008677:Metaphase / Q000187:drug effects; D051379:Mice; D013997:Time Factors
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins