Summary
The frequencies of common fragile sites (c-fra) induced in peripheral blood lymphocytes by fluorodeoxyuridine (FUdR), aphidicolin, or caffeine, in eight healthy controls were studied. There was a significantly higher frequency of breaks (P<0.05) in the latter two treatments than the former. Also, significant variation in total number of breaks was observed among the eight individuals within the three treatments. The relative frequency of a fragile site in relation to the total number of fragile sites in an individual rather than its expression in total cells was considered important. Use of a frequency of 4% or more of total fragile sites was proposed to eliminate apparent “random” breaks that were observed. Using these criteria, a total of 31 c-fra were observed in the three treatments. The distribution of the fragile sites was different in FUdR-treated cells as opposed to caffeine- and aphidicolin-treated cells. Sites 3p14 and 16q23 and Xp22 were the three most frequently observed c-fra. The higher frequency of expression of some fragile sites in normal controls, as observed here, suggests that any relationship between fragile sites and neoplastic transformation has to be carefully evaluated. A classification based on frequency in the population, rather than mode of induction, is suggested.
Similar content being viewed by others
References
Barbi G, Steinbach P, Vogel W (1984) Non random distribution of methotrexate-induced aberration on human chromosomes. Detection of further folic acid sensitive fragile sites. Hum Genet 68: 290–294
Berger R, Bloomfield CD, Sutherland GR (1985) Report of the committee on chromosome rearrangements in neoplasia and on fragile sites. (8th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 40:490–535
Chapelle A de la, Berger R (1984) Report of the committee on chromosome rearrangements in neoplasia and on fragile sites. (7th International Workshop on Human Gene Mapping). Cytogenet Cell Genet 37:274–311
Daniel A (1986) Clinical implications and classification of the constitutive fragile sites. Am J Med Genet 23:419–427
Daniel A, Ekblom L, Philips S (1984) Constitutive fragile sites 1p31, 3p14, 6q26 and 16q23 and their use as controls for false-negative results with fragile (X). Am J Med Genet 18:483–491
Das SK, Lau CC, Pardee AB (1984) Comparative analysis of caffeine and 3-aminobenzamide as DNA repair inhibitors in Syrian baby hamster kidney cells. Mutat Res 131:71–79
Glover TW (1981) FUdR induction of the X chromosome fragile site: evidence for the mechanism of folic acid and thymidine inhibition. Am J Hum Genet 33:234–242
Glover TW (1985) Biochemistry of fragile site expression. In: Sutherland GR, Hecht F (eds) Fragile sites on human chromosomes. Oxford University Press, New York, pp 80–94
Glover TW, Berger C, Coyle J, Echo B (1984) DNA polymerasealpha inhibition by aphidicolin induces gaps and breaks at common fragile sites in human chromosomes. Hum Genet 67:136–142
Hecht F (1986) Rare, polymorphic, and common fragile sites: a classification. Hum Genet 74:207–208
Hecht F, Sutherland GR (1984) Detection of the fragile X chromosome and other fragile sites. Clin Genet 26:301–303
Howard-Peebles PN (1981) Chromosome banding in X-linked mental retardation. Lancet I:494
Jacobs PA, Glover TW, Mayer M, Fox P, Gerard JW, Dunn HG, Herbst DS (1980) X-linked mental retardation. A study of seven families. Am J Med Genet 7:471–489
Shabtai F, Klar D, Nissimov R, Vardimon D, Hart J, Halbrecht I (1983) A new familial fragile site on chromosome 16(q23-24). Cytogenetic and clinical considerations. Hum Genet 64:273–276
Shabtai F, Hart J, Klar D, Halbrecht I (1986) Familial fragile site found at the cancer breakpoint (1)(q32). Inducibility by distamycin A, concomitance with fragile (16)(q22). Hum Genet 73:232–234
Smeets DCFM, Scheres JMJC, Hustinx TWJ (1986) The most common fragile site in man is 3p14. Hum Genet 72:215–220
Sutherland GR (1979) Heritable fragile sites on human chromosomes. II. Distribution, phenotypic effects, and cytogenetics. Am J Med Genet 31:136–148
Sutherland GR (1983) The fragile X chromosome. Int Rev Cytol 81:107–143
Sutherland GR, Hecht F (eds) (1985) Fragile sites on human chromosomes. Oxford University Press, New York
Sutherland GR, Parslow MI, Baker E (1985) New classes of common fragile sites induced by 5-azacytidine and bromodeoxyuridine. Hum Genet 69:233–237
Whang-Peng J, Bunn PA, Kao-Shan CS, Lee EC, Carney DN, Gazdar A, Minna JD (1982) A nonrandom chromosomal abnormality, del 3p(14–23) in human small cell lung cancer (CTCL). Cancer Genet Cytogenet 6:119–134
Yunis JJ, Soreng AL (1984) Constitutive fragile sites and cancer. Science 226:1199–1204
Zhou X, Xu B, Chu C, Xia G, Li N, Sha R (1984) Human chromosome hot-points. 1. Hotpoint at 3p14 in three populations. Hum Genet 67:249–251
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rao, P.N., Heerema, N.A. & Palmer, C.G. Fragile sites induced by FUdR, caffeine, and aphidicolin. Hum Genet 78, 21–26 (1988). https://doi.org/10.1007/BF00291228
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00291228