Effects of 5-fluorouracil or total-body irradiation on murine bone marrow microvasculature

This study was designed to investigate the changes in the murine bone marrow microvasculature following treatment with 5-fluorouracil (5-FU) or total-body irradiation (TBI). Seventy 8- to 12-week-old C3H male mice received either 5-FU at a dose of 150 mg/kg intravenously (i.v.) or TBI at a dose of 8 Gy in two fractions 4 hours apart. Femurs from the treated mice were studied by vascular casting, using mercox, and by routine histology at days 5, 21, and 90. On day 5, the sinusoids were markedly swollen, and many were fused with one another. This was accompanied by significant reduction in the bone marrow cellularity. The central sinus was grossly dilated in both TBI- and 5-FU-treated groups. The pronounced sinusoidal dilatation on day 5 appears to be a mechanical effect due to hematopoietic cell loss resulting in relative negative pressure outside the sinusoids. On day 21, the sinusoidal swelling had subsided, and the overall vascular volume appeared to be restored to normal. However, there was a large variation in the shape and size of the sinusoids, and those present were not uniformly distributed. This may be due to the result of mechanical pressure from the reconstituted hematopoietic cells. Whether these changes in the shape and distribution of sinusoids have functional significance--for instance, release of the hematopoietic cells into the circulation--remains to be established.