Skip to main content
Log in

Nonrandom distribution of methotrexate-induced aberrations on human chromosomes. Detection of further folic acid sensitive fragile sites

  • Original Investigations
  • Published:
Human Genetics Aims and scope Submit manuscript

Summary

Eleven folic acid sensitive fragile sites (3p14, 7p13, 7q31.1, 7q32, 9q32, 11p13, 14q23, 15q22, 16q23, Xp22.2, Xq22) were detected in one individual, eight of them previously unknown. These sites seem to bear each its specific sensitivity to folic acid deficiency. Six of the sites were observed simultaneously on both homologous chromosomes in at least one cell. Each of these 11 sites was also found in at least one among 12 individuals further examined. Some of these individuals showed six of these 11 sites. The fragile site 3p14 was detected in all individuals examined. The homologous sites 3p14 of one individual differed from each other in their frequency of lesions induced by methotrexate as well as fluorodeoxyuridine. This observation suggests that folic acid sensitivity is a property inherent in the chromatin of an individual chromosome at the site involved in fragility. This property seems to be responsible for the nonrandom fragility at that site and also for the individual sensitivity of each chromosomal site.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Benedict WF, Banerjee A, Gardner A, Jones PA (1977) Induction of morphological transformation in mouse C3H/10T1/2 clone 8 cells and chromosomal damage in hamster A(T)C1-3 cells by cancer chemotherapeutic agents. Cancer Res 37:2202–2208

    Google Scholar 

  • Das KC, Herbert V (1978) The lymphocyte as a marker of past nutritional status: persistence of abnormal lymphocyte deoxyuridine (dU) suppression test and chromosomes in patients with past deficiency of folate and vitamin B12. Br J Haematol 38:219–233

    Google Scholar 

  • de la Chapelle A, Berger R (1984) Los Angeles Conference 1983. Seventh international workshop on human gene mapping. Report of the committee on chromosomal rearrangements in neoplasia and on fragile sites. Cytogenet Cell Genet 37:274–311

    Google Scholar 

  • 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

    Google Scholar 

  • Goulian M, Bleile B, Tseng BY (1980) Methotrexate-induced misincorporation of uracil into DNA. Proc Natl Acad Sci USA 77:1956–1960

    Google Scholar 

  • Hecht F, Jacky PB, Sutherland GR (1982) The fragile X chromosome: current methods. Am J Med Genet 11:489–495

    Google Scholar 

  • ISCN (1978) An international system for human cytogenetic nomenclature (1978). Report of the standing committee on human cytogenetic nomenclature. Cytogenet Cell Genet 21:309–409

    Google Scholar 

  • Jennings M, Hall JG, Hoehn H (1980) Significance of phenotypic and chromosomal abnormalities in X-linked mental retardation (Martin-Bell or Renpenning syndrome). Am J Med Genet 7:417–432

    Google Scholar 

  • Krumdieck CL, Howard-Peebles PN (1983) On the nature of folicacid-sensitive fragile sites in human chromosomes: an hypothesis. Am J Med Genet 16:23–28

    Google Scholar 

  • Markkanen A, Heinonen K, Knuutila S, de la Chapelle A (1982) Methotrexate-induced increase in gap formation in human chromosome band 3p14. Hereditas 96:317–319

    Google Scholar 

  • Menzies RC, Crossen PE, Fitzgerald PH, Gunz FW (1966) Cytogenetic and cytochemical studies on marrow cells in B12 and folate deficiency. Blood 28:581–594

    Google Scholar 

  • 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

    Google Scholar 

  • Sutherland GR (1979) Heritable fragile sites on human chromosomes I. Factors affecting expression in lymphocyte culture. Am J Hum Genet 31:125–135

    Google Scholar 

  • Sutherland GR, Jacky PB, Baker E, Manuel A (1983) Heritable fragile sites on human chromosomes. X. New folate-sensitive fragile sites: 6p23, 9p21, 9q32, and 11q23. Am J Hum Genet 35:432–437

    Google Scholar 

  • Vorhees JJ, Janzen MK, Harrell ER, Chakrabarti SG (1969) Cytogenetic evaluation of methotrexate-treated psoriatic patients. Arch Dermatol 100:269–274

    Google Scholar 

  • Wegner RD (1983) A new inducible fragile site on chromosome 3(p14.2) in human lymphocytes. Hum Genet 63:297–298

    Google Scholar 

  • Welch JP, Winsor EJT, Camfield PR, Raftus RA (1982) Occurrence and possible significance of a “new” fragile site on chromosome 3. Am J Hum Genet 34:150A

    Google Scholar 

  • Glover TW, Berger C, Coyle J, Echo B (1984) DNA polymerase α inhibition by aphidicolin induces gaps and breaks at common fragile sites in human chromosomes. Hum Genet 67:136–142

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barbi, G., Steinbach, P. & Vogel, W. Nonrandom distribution of methotrexate-induced aberrations on human chromosomes. Detection of further folic acid sensitive fragile sites. Hum Genet 68, 290–294 (1984). https://doi.org/10.1007/BF00292586

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00292586

Keywords

Navigation