Relationship between chemical-induced fragile sites and chromosomal breakpoints in malignant cells in children.
Many fragile sites in the human genome occur at or near chromosomal breakpoints reportedly involved in translocations of DNA material in neoplastic cells. This fact has led some investigators to postulate that fragile sites have a pathogenic role in human neoplasia. To learn whether caffeine-induced fragile sites relate to breakpoints found in the neoplastic cells of an individual patient, we studied lymphocytes from the peripheral blood of 32 patients in remission from malignant disease. Lymphocytes were cultured in medium containing either 5-Fluoro-2'-deoxyuridine (FdU) or FdU plus caffeine, and G-banded metaphases were examined for nonrandom breaks. Analyses of completely G-banded malignant cell chromosomes from 31 of the 32 patients were available for comparison. In only once case, a 5-year-old child with acute lymphoblastic leukemia, did a caffeine-induced fragile site (1q44) coincide with a breakpoint in the neoplastic cells [dup(1)(q21-->q44)]. Our findings suggest that chromosomal abnormalities in childhood malignancies cannot generally be explained by the presence of FdU- or FdU plus caffeine-induced fragile sites.
Ribeiro
R C
RC
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Douglass
E C
EC
Williams
D L
DL
Raimondi
S C
SC
Valentine
M
M
Lewis
S
S
Crist
W M
WM
D000293:Adolescent; D000328:Adult; D002110:Caffeine / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D002877:Chromosomes, Human / Q000187:drug effects; D005260:Female; D005467:Floxuridine / Q000494:pharmacology; D015321:Gene Rearrangement; D006801:Humans; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured
D005467:Floxuridine; D002110:Caffeine