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Proliferative Kinetics and Chromosome Damage in Trisomy 21 Lymphocyte Cultures Exposed to -Rays and Bleomycin¹

Departments of Public Health [K. M., T. K., A. K.], and Maternal and Child Health [K. I.], Faculty of Medicine, University of Tokyo, Tokyo 113, Japan

Lymphocytes from patients with Down's syndrome (trisomy 21) have been investigated for cell cycle kinetics, cell proliferation delays, and chromosomal aberrations after exposure to -rays or bleomycin. Analysis by sister chromatid differential staining revealed that trisomy 21 lymphocytes started cell cycling about 5 hr earlier than did normal diploid lymphocytes after phytohe-magglutinin stimulation as a whole, but that cycling trisomic and normal cells had the same mean cell cycle times. When exposed to -rays or bleomycin in G₀, trisomy 21 lymphocytes showed a 30% or, on average, 50% longer duration of cell turnover times, respectively, than normal cells; only bleomycin-treated trisomic cells had a biphasic dose-response. Frequencies of dicentrics and rings in first-division cells after -ray or bleomycin exposure were twice as high in trisomic cells as in normal cells. The frequency of aberrations decreased by 50% (-ray-exposed) or 65 to 85% (bleomycin-treated) through successive divisions; trisomic cells showed a more marked decline in aberration yields compared to normal cells after bleomycin treatment. These data support the idea that circulating lymphocytes in trisomy 21 patients have a shorter average life span or a younger average age.

¹ Work supported by grants from the Ministry of Education, Science, and Culture of Japan.

² To whom requests for reprints should be addressed, at Department of Public Health, Faculty of Medicine, University of Tokyo, Bunkyo-Ku, Tokyo 113, Japan.

³ Present address: Department of Human Ecology, Kyorin University School of Health Sciences, Hachi-Ohji, Tokyo 192, Japan.

Received 7/ 6/83. Accepted 1/ 9/84.