Bone marrow evaluation

Mutagenicity tests with and without metabolic activation have been negative. Testing included Salmonella typhimurium assays, testing in Bacillus sub-tilis, and testing in V79 Chinese hamster cells. In addition, bone marrow evaluated after oral exposure was not reported to contain chromosomal damage. It was not reported to cause dominant lethal mutations in mice at 100 mg kg day... 

Because bone marrow evaluation is a critical part of immunotoxicity assessment, it is important that appropriate techniques be employed. The site of bone marrow collection, consistency in the collection, processing and evaluation of marrow, and expertise of the individual(s) evaluating each component of the assessment are important. 

The total amount of iron in the body is 4 to 5 g., a large percentage of this being present in hemoglobin. Iron is stored in the form of ferritin and hemosiderin in the liver, spleen, and bone marrow. Evaluation of the extent of iron stores may be made by estimating the amount of hemosiderin in bone marrow. The daily destruction and replacement of hemoglobin is about 7 to 8 g., which is the equivalent of a daily turnover of about 25 mg. of iron (Chapter 20). 

Current NKF guidelines define anemia as a hemoglobin (Hgb) level less than 11 g/dL (6.8 mmol/L).31 A number of factors can contribute to the development of anemia, including deficiencies in vitamin B12 or folate, hemolysis, bleeding, or bone marrow suppression. Many of these can be detected by alterations in RBC indices, which should be included in the evaluation for anemia. A complete blood cell count is also helpful in evaluating anemia to determine overall bone marrow function. 

Biopsy of tissue or bone marrow with pathologic evaluation... 

Flow cytometric evaluation of bone marrow and peripheral blood to characterize the type of leukemia, as well as to detect specific chromosomal rearrangements. The bone marrow at diagnosis usually is hypercellular, with normal hematopoiesis being replaced by leukemic blasts. The presence of greater than 20% blasts in the bone marrow is diagnostic for AML. 

Akagi et al. demonstrated the use of nanoparticles composed of amphiphilic poly (amino acid) derivatives as vaccine delivery and adjuvants [62, 102-104]. To evaluate the uptake of OVA encapsulated within y-PGA-Phe nanoparticles (OVA-NPs) by DCs, murine bone marrow-derived DCs were incubated with 250 nm-sized OVA-NPs for 30 min at 37 °C. The cells were then analyzed by flow cytometry (FCM) and confocal laser scanning microscopy (CLSM). OVA-NPs were efficiently taken up into DCs, whereas the uptake of OVA alone was barely detectable at the same concentration of OVA (Fig. 13). OVA-NPs were more efficiently taken up than OVA alone by DCs, and the uptake of OVA-NPs was inhibited at 4 °C. These results suggest that OVA-NPs were phagocytosed mainly via endocytosis by the DCs. In the case of OVA alone, an approximately 30-fold... 

Unexplained alterations in peripheral blood cell lines or histopathologic findings might suggest that cytologic evaluation of the bone marrow would be appropriate. 

The in vivo antitumor effects of interferons are believed to be related to both augmentation of natural killer cell activity and antiproliferative effects. Antiproliferative activity probably also accounts for the bone marrow suppression observed in some individuals given IFN and could potentially produce effects in a routine preclinical reproduction or teratology evaluation. Dosing studies performed in... 

Matter, B.E. and Grauwiler, J., Micronuclei in bone marrow cells. A simple in vivo model for the evaluation of drug-induced chromosomal aberrations, Mutat. Res., 23, 239,1974. 

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