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Chromosome Damage and Polyploidization Induced in Human Peripheral Leukocytes in Vivo and in Vitro with Nitrogen Mustard, 6-Mercaptopurine, and A-649

Dental Research Section (C.E.N.) and Hematology Section (H.H.S.), Veterans Administration Hospital, and University of Michigan School of Dentistry (C.E.N.) and Medical Center (Simpson Memorial Institute) (H.H.S.), Ann Arbor, Michigan

Chromosomal analysis of peripheral leukocytes in patients being treated with nitrogen mustard, 6-mercaptopurine, and A-649 demonstrated an increase in polyploidy, including cells showing endoreduplication. With nitrogen mustard, up to 15% of cells cultured were polyploids; with 6-mercaptopurine, 9% polyploidy was evident; and when A-649 was used, up to 14% polyploidy was seen. Chromosomal damage was evident with an increase in chromatid breaks and fragmentation. Dicentric chromosomes were the most common rearrangement found. These findings were not present in pretreatment cultures. When leukocytes from normal donors were incubated in vitro with these 3 agents, similar changes of polyploidization and structural abnormalities were produced. Care must be taken in the evaluation of chromosomal changes in patients undergoing active treatment.

Received 4/ 4/66. Accepted 6/17/66.