Radiobiological features of acute myeloblastic leukemia: comparison of self-renewal versus terminally differentiated populations.

PURPOSE: To evaluate the radiosensitivity of self-renewing progenitor cells in acute myeloblastic leukemia (AML), we have compared the radiosensitivity of the cells grown either in methylcellulose alone for 7 days, or first in suspension culture for 7 days before being plated in methylcellulose. Methylcellulose selects for terminal-dividing cells and suspension cultures have been developed because they allow self-renewal to occur: The exponential growth of the progenitors of AML cultured in suspension is due to self-renewal. METHODS AND MATERIALS: Cells were harvested from previously untreated leukemic human bone marrows. The myeloblastic lineage of the colonies was assessed by morphological, cytochemical, and immunophenotypic analysis, and by the use of growth factors that did not stimulate the growth of T-lymphocytes. The cell-cycle distribution of the blasts was analyzed by flow cytometry and was comparable for all samples. The irradiation was performed with gamma-photons at a dose-rate of 0.05 Gy/min, similar to the clinical conditions used in our institution for total body irradiation (TBI). RESULTS: The culture methods selected aggressive leukemias. There were large variations of the individual radiosensitivity whatever culture method was used. The progenitor cells capable of self-renewal were more radiosensitive than terminal dividing cells. In two cases, a shoulder was found in the initial part of the cell-survival curves of cells capable of self-renewal. In these two cases, the best fit for the data was the linear quadratic model (survival = e-alpha D-beta D2) with alpha/beta values of 1.49 Gy and 3.12 Gy, respectively. CONCLUSION: The very low values of alpha/beta suggest a reduced antileukemic effect in case of fractionated TBI, and may lead to more reliable screening methods to determine the most appropriate technique for radiation ablation of bone marrow prior to bone marrow transplantation (BMT).

Valorization of rapeseed meal. 2. Nutritive value of high or low-glucosinolate varieties and effect of dehulling.

Five groups of 12 growing rats each were fed a control diet or one of 4 experimental diets composed of either high glucosinolate (Jet Neuf) or low glucosinolate (Tandem) rapeseed meal. After a 3-day adaptation period, the rats were fed ad libitum for 15 days. Both meals were given dehulled or non-dehulled. The Tandem rapeseed meal provided all the protein and Jet Neuf half the protein of the corresponding diets. Dehulling the seeds significantly increased the energy and protein digestibility of the rapeseed meals (+ 16.5 and + 6.3 or 10.4 points, respectively), their digestible energy and digestible protein contents (+ 28 and + 30%) and metabolic utilization of digestible protein in the indirect nitrogen balance trial. Conversely, in the feeding trial, the feed efficiency of the dehulled meal diets was lower than that of the non-dehulled meal diets. However, dehulling the Tandem rape seeds did not seem to reduce lysine availability. Finally, feeding dehulled Tandem rapeseed meal as the sole protein source did not significantly increase the liver weight of the rats.