[The dynamic proliferative activity of mouse bone marrow cells during the suppression and recovery of hemopoiesis after 5-fluorouracil administration to the animals]

Abstract

Males of CBA x C57BL/F1 mice were given a single intravenous injection of 5-fluorouracil (5-FU; 0.15 mg/g of body weight), and their hematopoietic cell status was determined on days 2, 4, 7, 15 after 5-FU administration. Femoral cellularity and cycling cells were assessed in unfractionated bone marrow and cellular fractions separated by Percoll density gradient (fraction 2: 1.056 < P < 1.067 g/ml and fraction 3; 1.067 < P < 1.076 g/ml). To evaluate the functional status of cells that survived after the 5-FU administration, mice were given a second dose of 5-FU, 4 or 14 days after the first administration, or were subjected to X-irradiation (3.2 Gy), thermal burn (3-B rate on the crupper 1.2 x 1.2 mm) and X-irradiation plus the burn one day before sampling. It is shown that during a nadir period of hematopoiesis (4 days after 5-FU insult) the share of entry into the cycle is reduced in proliferating cells from a unfractionated bone marrow, from fraction 3, and the cycling fraction 2 up to 2.6, 4.0 and 17.4 per cent, compared to the norm (the pretreatment level). The cell populations selected by 5-FU become most sensitive to additional injuries (drug and physical stress-factors) 4 days after the first dose of 5-FU, but become resistant again to a second dose of 5-FU and the physical stress-factors 14 days after the first administration. The irradiation of mice as well as the thermal burn after 5-FU injection aggravate the effect of the latter, and X-irradiation+burn, on the contrary, reduce the severity of 5-FU after-effect.