The Lymphocyte as a Marker of Past Nutritional Status: Persistence of Abnormal Lymphocyte Deoxyuridine (dU) Suppression Test and Chromosomes in Patients with Past Deficiency of Folate and Vitamin B12*

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Abstract
In short‐term suspension cultures of bone marrow cells or PHA‐stimulated lymphocytes from normal subjects, non‐radioactive deoxyuridine (dU) suppresses the incorporation of radioactive thymidine ([3H]TdR) or its analogue, [125I]deoxyuridine ([125I]Udr), into DNA. This normal suppression by deoxyuridine (dU) is impaired in both of these cell systems from patients with deficiency of folate or vitamin B12, and corrected by the appropriate vitamin. Patients with megaloblastic anaemia due to deficiency of vitamin B12 or folate were studied before and after treatment. When treatment had returned to normal the bone marrow morphology and the serum and red cell vitamin levels, then the dU suppression test and chromosomal changes in the bone marrow were also corrected. However, the dU suppression test and chromosomal changes remained abnormal in lymphocytes as long as 84 d after therapy. These abnormal lymphocyte dU suppression tests were corrected by the appropriate in vitro additions of folic acid, methylfolate and vitamin B12, depending on the vitamin deficiency present before therapy. These studies suggest that an abnormal lymphocyte dU suppression test corrected by the appropriate vitamin in vitro, and characteristic chromosome abnormalities in lymphocytes, when these are absent in the bone marrow, indicate past deficiency of vitamin B12 or folate. These changes can be used for retrospective diagnosis of these deficiencies in patients treated by ‘shotgun’ therapy. They further support the concepts that circulating unstimulated lymphocytes: (1) do not incorporate appreciable amounts of vitamin B12 or folic acid; (2) reflect the vitamin status of the patient at the time the lymphocytes were generated; and (3) cannot replace bone marrow in dU suppression tests aimed at diagnosis of current marrow and other non‐lymphocyte cell line nutrient status. These studies add to the evidence that selective nutrient deficiency may occur in one but not another cell line in the same person, and point to the need for more studies on factors affecting nutrient delivery, uptake, and utilization by various human cell lines. These studies also provide a new approach to evaluation of circulating lymphocyte age.