Megaloblastic Maturation Masked by Iron Deficiency: a Biochemical Basis

S ummary In vitro bone marrow cultures, obtained from haematologically normal individuals and from patients with iron deficiency, were used to study the effect of the iron chelating agent, desferrioxamine, on the abnormal deoxyuridine suppression of 3 H‐thymidine incorporation into DNA produced by the dihydrofolate re‐ductase inhibitor, methotrexate. Desferrioxamine reduced the degree of impaired deoxyuridine suppression induced by methotrexate in marrow cultures of normal controls. However, in the iron‐deficient marrow cultures, the abnormal deoxyuridine suppression induced by methotrexate was less marked than that in controls, and desferrioxamine failed to reduce the degree of abnormal deoxyuridine suppression. After replacement of the iron stores, the degree of abnormal deoxyuridine suppression was increased, and desferrioxamine in this situation reduced the abnormal deoxyuridine suppression. In four marrow cultures obtained from patients with megaloblastic anaemia, the impaired deoxyuridine suppression in this situation was reduced towards normal by desferrioxamine. These findings provide biochemical evidence for the morphological findings of normoblastic maturation in vitamin B 12 ‐ or folate‐deficient states complicated by iron deficiency.