Linked Life Data

2409112

Source:http://linkedlifedata.com/resource/pubmed/id/2409112

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1985-7-30
pubmed:abstractText
To determine the influence of cell cycle-specific agents on primate hematopoiesis and fetal hemoglobin production, two juvenile cynomolgus monkeys (Macaca fascicularis) were repeatedly bled to maintain their hemoglobins at approximately 6.5 g/dl and fetal hemoglobin levels at 3-5%. Six separate 5-d courses of hydroxyurea at 100 mg/kg per d were then administered over the next 200 d while phlebotomy was continued. These courses of hydroxyurea progressively raised the fetal hemoglobin levels to 17 and 18%, respectively. The drug had very little effect on the frequency of immature erythroid progenitors (BFU-E) in the bone marrow, but caused a marked reduction in the frequency of later progenitors (CFU-E) and a transient fall in the reticulocyte count. Following the courses of hydroxyurea, the number of F cells and the fetal hemoglobin level fell to base line over a period of 4 wk. Two control animals which were not phlebotomized showed no detectable increase in F cells or fetal hemoglobin when treated with the same regimen of hydroxyurea. A 5-d course of 5-azacytidine at 8 mg/kg per d was then given to each of the phlebotomized animals. This produced a more profound, albeit transient, reticulocytopenia, a fall in the CFU-E/BFU-E ratio, and a prompt increase in the fetal hemoglobin to levels even higher than were seen following a single 5-d course of hydroxyurea at 100 mg/kg/d. Subsequently, the animals were given a single dose of vinblastine at 0.4 mg/kg which reduced reticulocytes and CFU-E to the same extent as hydroxyurea; however, vinblastine at this dose had no effect on hemoglobin F (HbF) production. In contrast, when vinblastine was administered to the phlebotomized monkeys as a 5-d course at 0.2 mg/kg/d, prolonged reticulocytopenia followed by dramatic F cell and HbF responses were seen. Combinations of single dose vinblastine and a 5-d course of hydroxyurea were subsequently administered using two different schedules. When the animals received vinblastine on the first day of a 5-d course of hydroxyurea, the F cell response was double that seen following hydroxyurea treatment alone. In contrast, when vinblastine was administered on the final day of hydroxyurea treatment, the magnitude of the F cell response was the same as that which occurred following hydroxyurea treatment alone, but the onset of the rise was delayed for 4 d and HbF/F cell response was much higher. These results establish several important features of the fetal hemoglobin response to cytotoxic agents in the primate model. The response requires accelerated erythropoiesis and is preceded by transient reticulocytopenia. The response is produced by S phase- and M phase-specific agents when given in sufficient doses and at appropriate schedules. Passage of erythrocyte progenitors through M phase appears to be necessary for expression of the effect produced by S phase agents. The fetal hemoglobin response induced by cytotoxic drug administration occurs during the recovery of erythropoiesis following marrow suppression.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-115514, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-1166074, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-444655, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-4822532, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-5159846, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-5671289, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-57826, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-6030567, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-6156625, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-6181096, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-6181507, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-6183586, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-6192443, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-6197114, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-6198655, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-6198662, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-6199670, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-6200940, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-6205021, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-621285, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-6693439, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-6950945, http://linkedlifedata.com/resource/pubmed/commentcorrection/2409112-884703
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9738
pubmed:author
pubmed:issnType
Print
pubmed:volume
75
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1999-2005
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1985
pubmed:articleTitle
Influence of cell cycle phase-specific agents on simian fetal hemoglobin synthesis.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't