Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598766 (leukemogenesis)
 4,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of leupeptin on the induction of lymphoblastic leukemia in ICR/JCL female mice by N-nitrosobutylurea (NBU) was investigated. NBU was given as a 0.02% solution in drinking water for 10 weeks. A 0.1% concentration of leupeptin was given in the diet. Group A was fed on the leupeptin diet from the beginning, Group B received it after the end of NBU treatment, and Group C was fed on a leupeptin-free control diet throughout. The average periods in the appearance of leukemia in groups A, B, and C were 115+/-50, 112+/-43, and 100+/-17 days (mean+/-SD), respectively, and there was a significant difference between groups A and B and Group C at P less than 0.001. In regard to this point, leupeptin might have the effect of retarding the rpocess of leukemogenesis. However, leupeptin showed no effect on the incidence and histopathological finding of leukemia.
 ...
PMID:Effect of leupeptin on induction of lymphoblastic leukemia in mice by N-nitrosobutylurea. 26 41

The spontaneous colony (SC)-forming activity of bone marrow cells of rats during butylnitrosourea (BNU) treatment was studied sequentially in an attempt to analyze stages of leukemogenesis. Aspirated bone marrow cells from female Sprague-Dawley (SD) rats that had been given continuous access to drinking water containing 400 ppm BNU were examined at intervals of 3-5 weeks for colony formation of granulomonocytic cells with or without supplemental colony-stimulating factor (CSF). Granulocytic leukemia was first observed at week 12, and the cumulative incidence reached 80% by week 30. SCs were obtained in 56% of rats in the early stage (3 weeks) and in up to 59% of rats in the late stages (20-25 weeks). However, in the middle stages colony formation was rare, even with the addition of CSF. When adherent cells were removed from the bone marrow cells, the SC-forming activity in the early stage was almost entirely lost, whereas much of that in the late stage remained. It is possible that in the former case, overproduction of endogenous CSF by adherent cells under the influence of BNU treatment could be involved. In contrast, late stage SC formation may be associated with the generation of altered cells, including leukemic or preleukemic elements, which have increased capacity for autonomous growth. The loss of SC-forming activity in the middle stage appeared to be attributable to an extreme reduction in endogenous CSF due to marked devastation of the bone marrow. Technical improvement in adjusting more precisely the level of CSF in the culture medium is required to enable further analysis of leukemogenesis, focused on the colony-forming activity of target cells.
 ...
PMID:Sequential study on spontaneous colony formation by bone marrow cells during butylnitrosourea-induced leukemogenesis in the rat. 231 3

BDF1 mice were exposed to butylnitrosourea for 12 weeks (BNU, 0.02% in the drinking water) and died of thymic lymphomas with median latency periods of 12-20 weeks. In addition to BNU, groups of mice received weekly radiation doses of 0.0625-1.0 Gy; 12 X 0.25 Gy enhanced leukemogenesis, 12 X 0.75 Gy delayed it and 12 X 0.50 Gy had no effect. Lower doses had marginal enhancing effects. After a dose of 12 X 1.0 Gy, the mice died earlier than after treatment with BNU alone and, as with 12 X 0.75 Gy, some extrathymic lymphomas were observed. The numbers of CFU-S in the femur and the spleen showed a dose-dependent depression, in addition to the effect of BNU alone. In lymphocyte stimulation assays with Con A und LPS and also in the mixed lymphocyte reaction, a reduced proliferation was found, again dependent on the radiation dose. Therefore, there was no correlation of leukemogenesis and the degree of stem-cell reduction or depression of these immune parameters. The delay of leukemogenesis by 12 X 0.75 Gy in addition to BNU may be caused by an enhanced target cell kill.
 ...
PMID:Effects of radiation on murine T-cell leukemogenesis induced by butylnitrosourea. 660 33

A total of 8,229 C57 Black mice of both sexes were randomly assigned to various groups. In some groups, mice aged 33 +/- 3 days were submitted to either sham, neutron or cobalt external radiation at 32, 45, 63, 88 and 123 mGy or at 18, 25, 36 and 51 cGy dose levels, respectively. In other groups, mice either at birth or weaning, were injected with tritiated thymidine or tritiated water, or were given tritiated water as drinking water for the entire lifespan. The main purpose of the experiment was to investigate the low dose-response relationship of cancer induction, especially leukemogenesis and to evaluate the excess risk, using actuarial age-specific rates. Following neutron or cobalt exposure, the phenotypic occurrence of lymphocytic lymphomas was earlier in appearance and higher in yield during the first decades of lifespan in irradiated groups versus matching controls, whereas such occurrence was markedly lower in yield at a later age. Under parallel experimental conditions, induction of reticulum cell lymphomas, however, was uniformly enhanced throughout the entire lifespan. Induction rates of all tumors (reticular and solid) pooled were significantly increased, and more so following cobalt than neutron irradiation. In mice injected with tritiated thymidine, the overall tumor incidence was increased monotonically throughout the lifespan. In mice exposed to tritiated water, the incidence of lymphocytic lymphomas was markedly increased throughout the lifespan, whereas no such effect was observed for reticulum cell tumors. In the light of tumor data analysis, it appears that selection of a particular type of tumor as a dependent variable for dose-response assessment cannot disregard the primary modulation of the whole tumor spectrum, In C57 Black murine leukemogenesis, the shape and structure of the dose-response regression curve over the entire lifespan dose not fit the linear-quadratic model. It is, however, theorized that our data are consistent with the two-mutation clonal expansion model, assuming creation of initiated cells which are added to the pool of spontaneously occurring initiated cells and implying that the excess risk is initially high at early age and then decreases with increasing age following exposure. It is concluded that murine radiocarcinogenesis investigation may contribute to improving the assessment as well as understanding the underlying mechanisms of low level radiation hazards.
 ...
PMID:Time sequence of cancer occurrence. Implications in low level radiation risk assessment. 1019 72

High environmental tungsten levels were identified near the site of a childhood pre-B acute lymphoblastic leukemia cluster; however, a causal link between tungsten and leukemogenesis has not been established. The major site of tungsten deposition is bone, the site of B-cell development. In addition, our in vitro data suggest that developing B lymphocytes are susceptible to tungsten-induced DNA damage and growth inhibition. To extend these results, we assessed whether tungsten exposure altered B-cell development and induced DNA damage in vivo. Wild-type mice were exposed to tungsten in their drinking water for up to 16 weeks. Tungsten concentration in bone was analyzed by inductively coupled plasma mass spectrometry and correlated with B-cell development and DNA damage within the bone marrow. Tungsten exposure resulted in a rapid deposition within the bone following 1 week, and tungsten continued to accumulate thereafter albeit at a decreased rate. Flow cytometric analyses revealed a transient increase in mature IgD(+) B cells in the first 8 weeks of treatment, in animals of the highest and intermediate exposure groups. Following 16 weeks of exposure, all tungsten groups had a significantly greater percentage of cells in the late pro-/large pre-B developmental stages. DNA damage was increased in both whole marrow and isolated B cells, most notably at the lowest tungsten concentration tested. These findings confirm an immunological effect of tungsten exposure and suggest that tungsten could act as a tumor promoter, providing leukemic "hits" in multiple forms to developing B lymphocytes within the bone marrow.
 ...
PMID:In vivo tungsten exposure alters B-cell development and increases DNA damage in murine bone marrow. 2315 88