Incorporation of Radioactive L-Cystine by Normal and Leukemic Leukocytes in Vivo

Methods for studying the in vivo incorporation of radioactive amino acids by leukocytes are described. The incorporation of S³⁵ L-cystine into normal and leukemic leukocytes was studied and compared with the utilization of S³⁵ L-methionine, S³⁵ sodium sulfate, and C¹⁴ sodium formate.

Radioactive L-cystine is rapidly absorbed and rapidly incorporated into the proteins of leukocytes. There are distinctive differences in rates and levels of utilization of S³⁵ L-cystine by normal leukocytes and by leukocytes of acute and chronic leukemia.

The leukocytes of acute leukemia and of chronic myeloid leukemia have a greater avidity for L-cystine than normal leukocytes. This rapid utilization of an amino acid by immature leukocytes is not limited to L-cystine and is probably a manifestations of the rapid metabolic turnover characteristic of immature cells in general. However, in view of the observations on the specificity of L-cysteine and related compounds in modifying the leukotoxic effects of nitrogen mustard, the avidity of immature leukocytes for L-cystine may have greater significance than the utilization of other metabolites.

The data indicate that the life span of normal leukocytes is approximately 13 days. The life span of leukocytes in chronic myeloid leukemia is slightly less than that of normal leukocytes whereas the life span of acute leukemic leukocytes is much shorter than that of normal leukocytes. The life span of lymphocytes in chronic lymphatic leukemia appears to be much longer than that of normal leukocytes. Although L-cystine and L-methionine are readily utilized its acute leukemia, there is marked impairment in the utilization of sodium sulfate in vivo. By comparison, normal leukocytes readily utilize sodium sulfate in vivo. This discrepancy may be due to the rapid turnover of sulfur in acute leukemia or to an intrinsic metabolic defect of acute leukemic leukocytes.