Lifetime treatment of mice with azidothymidine (AZT) produces myelodysplasia.
AZT has induced a macrocytic anemia in AIDS patients on long term AZT therapy. It is generally assumed that DNA elongation is stopped by the insertion of AZT into the chain in place of thymidine thus preventing the phosphate hydroxyl linkages and therefore suppresses hemopoietic progenitor cell proliferation in an early stage of differentiation. CBA/Ca male mice started on AZT 0.75 mg/ml H2O at 84 days of age and kept on it for 687 days when dosage reduced to 0.5 mg/ml H2O for a group, another group removed from AZT to see recovery, and third group remained on 0.75 mg. At 687 days mice that had been on 0.75 mg had average platelet counts of 2.5 x 10(6). Histological examination on 9 of 10 mice with such thrombocytopenia showed changes compatible with myelodysplastic syndrome (MDS). A variety of histological patterns was observed. There were two cases of hypocellular myelodysplasia, two cases of hypersegmented myelodysplastic granulocytosis, two cases of hypercellular marrow with abnormal megakaryocytes with bizarre nuclei, one case of megakaryocytic myelosis associated with a hyperplastic marrow, dysmyelopoiesis and a hypocellular marrow and two cases of myelodysplasia with dyserythropoiesis, hemosiderosis and a hypocellular marrow. Above mentioned AZT incorporation may have induced an ineffective hemopoiesis in the primitive hemopoietic progenitor cells, which is known to be seen commonly in the myelodysplastic syndrome.
Inoue
T
T
Department of Pathology, Yokohama City University School of Medicine, Japan.
Cronkite
E P
EP
Hirabayashi
Y
Y
Bullis
J E
JE
Mitsui
H
H
Umemura
T
T
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000748:Anemia, Macrocytic / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D003114:Colony-Forming Units Assay; D004906:Erythrocyte Count / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors; D015215:Zidovudine / Q000009:adverse effects / Q000633:toxicity*
D019380:Anti-HIV Agents; D015215:Zidovudine