Abstract
Roberts syndrome (RS) is a rare autosomal recessive disorder characterized by pre- and postnatal growth retardation, limb reduction abnormalities, and craniofacial anomalies. Mitotic chromosomes from RS individuals display repulsion of heterochromatin regions or centromere splitting, leading to a railroad-track appearance of mitotic chromosomes. Abnormalities in metaphase duration, anaphase progression, nuclear morphology, and increased frequency of micronucleation have been reported in RS cells. Cells from RS heterozygotes are normal in these respects, and in vitro complementation of the defects in somatic cell hybrids has been reported. Therefore, in preparation for the isolation of cDNAs that complement the RS defect, we investigated various drug treatments to identify an agent that specifically involves the growth of RS cells. Based on the cytogenetic and cell biologic findings, we chose agents that increase micronucleation or inhibit protein synthesis. We found that RS cells are hypersensitive to gamma radiation, mitomycin C, G418 and hygromycin B, but not to colcemid or streptonigrin when compared to normal cells. DNA content and cell viability analysis confirmed that the sensitivity to gamma irradiation was primarily due to increased cell death.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Literature cited
Van Den Berg, D., and Francke, U. (1993).Am. J. Med. Genet. (in press).
Levy, M., Sacrez, R., Luckel, J.C., Warter, S., Stoll, C., and Szwarcberg, R. (1972).Ann. Pediatr. 19314–320.
Judge, C. (1973).Med. J. Aust. 2280–281.
German, J. (1979).Clin. Genet. 16441–447.
Louie, E., and German, J. (1981).Clin. Genet. 1971–74.
Tomkins, D., Hunter, A., and Roberts, M. (1979).Am. J. Med. Genet. 417–26.
Krassikoff, N.E., Cowan, J., Parry, D.M., and Francke, U. (1986).Am. J. Hum. Genet. 39618–630.
Tomkins, D.J., and Sisken, J.E. (1984).Am. J. Hum. Genet. 361332–1340.
Louie, E., and German, J. (1983).J. Cell Biol. 97:192A.
Jabs, E.W., Tuck-Muller, C., Cusano, R., and Rattner, J.B. (1991).Chromosoma 100251–261.
Pincu, M., Callisen, H., and Norman, A. (1985).Int. J. Radiat. Biol. 47423–432.
Thomson, E.J., and Perry, P.E. (1988).Mutagenesis 3415–418.
Yamamoto, K.I., and Kikuchi, Y. (1980).Mutat. Res. 71127–131.
Hogstedt, B., and Karlsson, A. (1985).Mutat. Res. 156229–232.
Ramudu, K. (1991).Cell. Mol. Biol. 37139–147.
Wakata, A., and Sasaki, M.S. (1987).Mutat. Res. 7151–57.
Cabañas, M., Vazquez, D., and Modolell, J. (1978).Eur. J. Biochem. 8721–27.
Davies, J., and Jimenez, A. (1980).Am. J. Trop. Med. Hyg. 291089–1092.
González, A., Jimenez, A., Vazquez, D., Davies, J.E., and Schindler, D. (1978).Biochim. Biophys. Acta 521459–469.
Ward, J.F. (1975).Adv. Rad. Biol. 5181.
Lown, J.W. (1983).Mol. Cell. Biochem. 5517–40.
Durse, L., Covey, J.M., Collins, C., and Sinha, B.K. (1989).Chem. Biol. Interact. 7163–78.
Durse, L., Rajagopalan, S., Eliot, H.M., Covey, J.M., and Sinha, B.K. (1990).Cancer Res. 50648–652.
Burns, M.A., and Tomkins, D.J. (1989).Mutat. Res. 216243–249.
Ishioka, C., Kanamuru, R., Konishi, Y., Ishikawa, A., Shibata, H., and Wakui, A. (1990).Cancer Chemother. Pharmacol. 26117–121.
von Sonntag, C. (1991).Basic Life Sci. 58287–317.
Van Den Berg, D.J., and Francke, U. (1991).Am. J. Hum. Genet. 49:421S.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Van Den Berg, D.J., Francke, U. Sensitivity of Roberts syndrome cells to gamma radiation, mitomycin C, and protein synthesis inhibitors. Somat Cell Mol Genet 19, 377–392 (1993). https://doi.org/10.1007/BF01232749
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01232749