Abstract
The fragile sites at 10q25, 16q22, and 17p12 can all be induced in lymphocyte culture by BrdU or BrdC added 6-12 hrs prior to harvest. Without induction, fra(10)(q25) is rarely expressed spontaneously, whereas fra(16)(q22) is frequently expressed spontaneously. Fra(17)(p12) is frequently expressed spontaneously but is probably expressed only after induction in some individuals. Distamycin A, netropsin, and Hoechst 33258 induced high levels of expression of fra(16)(q22) and fra(17)(p12) but did not enhance expression of fra(10)(q25). The mechanisms of induction of fra(16)(q22) by BrdU and distamycin A appear to be different, since the time of induction by BrdU reaches a maximum about 12 hrs prior to harvest whereas induction by distamycin A requires much longer exposure. The fragile sites at 10q25 and 16q22 were both induced in fibroblast culture by BrdU. Fra(17)(p12) is accepted as a fragile site because preliminary studies show that it behaves similarly in lymphocyte culture to fra(16)(q22); however, there is only limited evidence for fragility at 17p12.
MeSH Terms
Bisbenzimidazole/pharmacology
Bromodeoxycytidine/pharmacology
Bromodeoxyuridine/pharmacology
Cells, Cultured
Chromosome Fragile Sites
Chromosome Fragility
Chromosomes, Human, 16-18
Chromosomes, Human, 6-12 and X
Distamycins/pharmacology
Dose-Response Relationship, Drug
Female
Gene Expression Regulation
Humans
Lymphocytes/ultrastructure
Male
Chemicals
Distamycins
Bromodeoxycytidine
stallimycin
Bromodeoxyuridine
Bisbenzimidazole
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sutherland G R
Jacky P B
Baker E G
References (20)
20 references, click to expand
-
Mechanisms of chromosome banding. VIII. Hoechst 33258-DNA interaction.
Chromosoma. 1975 Oct 14;52(3):229-43
PMID: 1183300
-
Bromodeoxyuridine mutagenesis in mammalian cells is related to deoxyribonucleotide pool imbalance.
Mol Cell Biol. 1981 Mar;1(3):254-60
PMID: 6965099
-
Direct evidence for the role of incorporated BUdR in the induction of sister chromatid exchanges.
Exp Cell Res. 1978 Nov;117(1):23-30
PMID: 720406
-
Effects of distamycin A on human leukocytes in vitro.
Cytogenet Cell Genet. 1979;23(1-2):103-7
PMID: 83927
-
Heritable fragile sites on human chromosomes I. Factors affecting expression in lymphocyte culture.
Am J Hum Genet. 1979 Mar;31(2):125-35
PMID: 36752
-
Heritable fragile sites on human chromosomes II. Distribution, phenotypic effects, and cytogenetics.
Am J Hum Genet. 1979 Mar;31(2):136-48
PMID: 453198
-
Influence of nucleotide sequence on dA.dT-specific binding of Netropsin to double stranded DNA.
Nucleic Acids Res. 1979 Jun 25;6(8):2831-7
PMID: 461206
-
Expression in fibroblast culture of the satellited-X chromosome associated with familial sex-linked mental retardation.
Hum Genet. 1980 Feb;53(2):267-9
PMID: 6928413
-
Heritable fragile sites on human chromosomes. V. A new class of fragile site requiring BrdU for expression.
Am J Hum Genet. 1980 Jul;32(4):542-8
PMID: 7395866
-
Demonstration of a heritable fragile site in human chromosome 16 with distamycin A.
Cytogenet Cell Genet. 1980;28(1-2):87-94
PMID: 7449440
-
5-Bromodeoxycytidine in the study of sister chromatid exchanges in human lymphocytes.
Hum Genet. 1980;55(2):259-63
PMID: 7450769
-
Hoechst 33258 induced uncondensed sites in marsupial chromosomes.
Chromosoma. 1981;83(2):249-62
PMID: 6168441
-
Heritable fragile sites on human chromosomes. IX. Population cytogenetics and segregation analysis of the BrdU-requiring fragile site at 10q25.
Am J Hum Genet. 1982 Sep;34(5):753-6
PMID: 7124730
-
Chromosome 17 has a real fragile site at p12.
Hum Genet. 1982;61(2):177-9
PMID: 7129447
-
Map of distamycin, netropsin, and actinomycin binding sites on heterogeneous DNA: DNA cleavage-inhibition patterns with methidiumpropyl-EDTA.Fe(II).
Proc Natl Acad Sci U S A. 1982 Sep;79(18):5470-4
PMID: 6291045
-
Spontaneous expression of the chromosome fragile site fra(10)(q25).
Am J Hum Genet. 1983 Jan;35(1):123-5
PMID: 6823968
-
Expression of fragile site at 10q25 in normal culture conditions.
Am J Hum Genet. 1983 Jan;35(1):126-7
PMID: 6823969
-
BrdU-sensitive fragile site on long arm of chromosome 16.
Am J Hum Genet. 1983 May;35(3):530-3
PMID: 6859046
-
The fragile X chromosome.
Int Rev Cytol. 1983;81:107-43
PMID: 6347931
-
Comparisons of in vivo BrdU labeling methods and spontaneous sister chromatid exchange frequencies in regenerating murine liver and bone marrow cells.
Chromosoma. 1978 Sep 11;68(4):303-11
PMID: 81738