Prolonged Survival of Lymphocytes With Chromosomal Defects in Children Treated With 1,3-Bis(2-Chloroethyl)-1-Nitrosourea

Summary

Chromosomal defects were observed in as many as 65% of the cultured circulating leukocytes of 6 children with acute leukemia and 2 with Ewing's sarcoma of the femur who were treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a lipid-soluble alkylating agent. These defects, which included breaks in chromatids and chromosomes and interchanges of chromatin between 2 or more chromosomes to form triradials, quadriradials, and other multibranched chromosomes, persisted for 1–11½ months after BCNU therapy. The other chemotherapeutic agents and previous diseases of these patients are unlikely to have produced these defects, since a similar group of control patients had no significant number of chromosomal defects in their cultured leukocytes. Identical defects were produced by in vitro BCNU treatment of cultured leukocytes from 2 normal adults. In vitro studies also showed that BCNU affects all chromosomes randomly; however, the effects do not appear immediately after treatment. These chromosomal defects were found only in cells presumed to be lymphocytes in spite of BCNU's lethal effect on many cell types. This specificity may be more apparent than real and secondary to known characteristics of lymphocytes and their response to phytohemagglutinin. Despite the large number of agents capable of damaging chromosomes, only irradiation and, recently, lysergic acid diethylamide have been reported to produce defects which persist for long periods following in vivo therapy.