Leukocyte kinetics studied by nitrogen mustard induced alterations in DNA phosphorus labeling.

By RICHARD I. WALKER, J. C. HERION AND J. G. PALMER C URRENT EVIDENCE indicates that isotopic labeling of deoxyribonucleic acid ( DNA ) results from synthesis during mitotic interphas&5 and that acquired label is retained until cell death and degradation occur.”5 2 The validity of using inorganic radiophosphorus ( p:oi ) as a leukocyte DNA label rests on these findings. Leukocyte kinetics have been studied by a number of investigators using DNA P:i2 labeIing.12’7 ’1 ’6 Such studies have shown a rise in concentration of label in circulating leukocyte DNA-P for several days after P32 administration, reaching i peak at a time which varies in different species. Decline in label concentration has been more gradual than the rate of increase. In rabbits, DNA-P specific activity of total leukocytes remains at a low level for at least two days, climbs sharply to reach a peak four days after p32 administration, and then declines gradually. Lymphocyte DNA-P activity remains at a nearly cOflstIIlt low level during this time, contributing nothing to the general shape of the curve for total leukocytes.17 Although the peak in circulating leukocyte DNA-P specific activity seems to be produced by events occurring during the first two hours after injection of the isotope,15 continued labeling of DNA persists for several days after a single intravenous injection of only two microcuries ( .tc. ) of inorganic P32!Kg.17 and contributes significantly to the shape of the curve at least during the period after the peak. Although nitrogen mustard ( HN ) has generally been considered to act primarily as an inhibitor of cell production,19’2#{176} Osgood and Chu21 showed in cultures of marrow cells that in concentrations of 1 : 500,000 or greater it regularly killed all granulocvtic elements thought capable of mitosis but did not