Distribution of X-ray-induced chromosome breakpoints in Down syndrome lymphocytes.
Down syndrome (DS) individuals are known to be predisposed to develop leukemia and their lymphocytes are highly sensitive to the induction of chromosome aberrations by X-rays. A study was conducted to identify the chromosome breakpoints and to evaluate whether site specificity for chromosome breakage and rearrangement may exist which may explain the predisposition phenomenon. DS lymphocytes at the G1 phase of the cell cycle were irradiated with 300, 450, and 600 rad of X-rays. Cells were harvested after 3 days in culture and 193 G-banded karyotypes were analyzed to identify the induced chromosome abnormalities. Out of 273 breakpoints identified, 122 were involved in the formation of stable chromosome rearrangements and 151 in the formation of unstable abnormalities. The Poisson analysis of these breakpoints demonstrated that 16 chromosome bands located in chromosomes 1, 3, 7, 12, 17, 19 and X were preferentially involved in breakage and rearrangement (P less than 0.05). These 16 bands are also found to be locations of "cancer breakpoints," oncogenes, or fragile sites. Many abnormal cells were observed to carry stable chromosome rearrangements only. Therefore, these cells are presumed to be compatible with survival and to be "initiated" in the transformation process. We propose that similar stable and site-specific chromosome rearrangements may exist in proliferating cells in DS individuals after exposure to clastogens and that this abnormality predisposes them to develop leukemia.
Shafik
H M
HM
Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77550.
Au
W W
WW
Whorton
E B
EB
Legator
M S
MS
D002478:Cells, Cultured; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D002877:Chromosomes, Human / Q000528:radiation effects*; D004314:Down Syndrome / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007621:Karyotyping; D008214:Lymphocytes; D008297:Male