Leukocyte Kinetics Studied by Nitrogen Mustard Induced Alterations in DNA Phosphorus Labeling

Abstract

Abstract The effect of a large dose of nitrogen mustard on total and differential leukocyte counts in rabbits has been studied in conjunction with the effect on DNA labeling with inorganic radiophosphorus. Considered together, the findings indicate that this dose of nitrogen mustard has a direct lethal effect on lymphocytes and effectively blocks P32 incorporation into leukocyte DNA for several days by killing the elements capable of division. The post-mitotic granulocyte reservoir seems to remain intact and is of sufficient size to replace those lost from the circulation for about 56 hours. Granulocyte circulating half-time under the conditions of these experiments falls between two and seven hours. The post-mitotic granulocyte reservoir is calculated to be 40 times the size of the circulating pool. During the period of rapid granulocyte recovery, leukocytes have been shown to exhibit a decreasing concentration of DNA label per element and maintainence of the same level of label per element depending on the availability of precursor P32. At present no conclusion about DNA labeling characteristics with inorganic P32 under steady state conditions is warranted.