Effects of Cyclophosphamide on Lymphoid Tissues Labelled with 5-Iodo-2-Deoxyuridine-125I and 51Cr

Abstract

The effect of cyclophosphamide (CY) 300 mg/kg was observed on lymphoid tissue labelled with 5-iodo-2-deoxyuridine-125I (I-UDR). A generalized reduction was observed in the radioactivity in all lymphoid tissue, but the greatest effect was on the thymus and bone marrow. Nucleic acid synthesis as assessed by I-UDR uptake by these tissues remained suppressed for 3 days in lymph nodes, spleen and bone marrow. Recovery was followed by a period of increased synthesis, returning to normal by 14 days. DNA synthesis in the thymus remained suppressed for as long as 10 days. CY produced a fourfold reduction in the proportion of transfused I-UDR labelled lymphocytes that localize in lymph nodes and the spleen. There was no evidence of deviation to other organs. No similar reduction was found in lymphocytes labelled with 51Cr. It was, therefore, concluded that CY is selectively cytotoxic to those lymphocytes which are short-lived and have a more rapid rate of turnover in the peripheral lymphoid tissues. This could account for its preferential effect in depleting lymphoid tissue of B-lymphocytes, and for the marked intensificatiOn of contact sensitivity reactions in guinea pigs pretreated with this drug.