Increased Radiosensitivity of Cell Lines Derived From a Down's Syndrome Patient With Ocular Telangiectasia

Abstract

Studies on radiosensitivity of cells from Down's syndrome (DS) patients were stimulated by the observation of their increased susceptibility to leukemia. While lymphocytes from DS patients were found to consistently show increased chromosomal aberrations after exposure to ionizing radiation, conflicting reports have been published on the radiosensitivity of fibroblasts and lymphoblastoid cell lines (LCL) derived from these patients. In the present study, cultured skin fibroblast lines developed from a DS patient with ocular telangiectasia and five normal subjects were compared for both cell killing and chromosomal aberrations (breaks, translocations, inversions, dicentrics, and rings) after low dose-rate γ-irradiation. The LCLs developed from the patient and two normal persons were also compared for chromosomal radiosensitivity using the same irradiation protocol. A comparison of the D10 (radiation dose resulting in 10% survival) values estimated from the survival curves and the frequencies of induced chromosome aberrations in different cell lines showed that the DS cells were more radiosensitive than the respective controls. The increased cellular radiosensitivity of the DS patient reported here could be due to a combination of genetic factors (DS plus a gene for hypersensitivity to radiation) and, thus, may not be representative of all DS patients. Alternatively, the use of low dose-rate irradiation could be a factor in revealing the radiosensitivity of DS fibroblasts in general. (J Child Neurol 1992;7(Suppl):S83-S87.)

References

Opitz JM

Gilbert-Barness EF

: Reflections on the pathogenesis of Down Syndrome. Am J Med Genet1990;(Suppl 1):38-51.

Montagna D.

Maccario R.

Ugazio AG

, et al: Cell mediated cytotoxicity in Down syndrome: Impairment of allogenic mixed lymphocyte reaction, NK and NK like activities. Eur J Pediatr1988;148:53-57.

Conen PE

Erkman B.

: Combined mongolism and leukemia: Report of 8 cases with chromosome studies. Am jDis Child1966;112:429.

Miller RW

: Neoplasia and Down's syndrome. Ann NY Acad Sci1970;171:637.

Percy ME

Dalton AJ

Markovic VD

, et al: Red cell superoxide dismutase, glutathione peroxidase and catalase in Down syndrome patients. Am J Med Genet1990;35:459-467.

Todaro GJ

Martin GM

: Increased susceptibility of Down's syndrome fibroblasts to transformation by SV40. Proc Soc Exp Biol Med1967;124:1232-1236.

Chudina AP

Malvutina TS

Pogosyants HE

: Comparative radiosensitivity of chromosome in the cultured peripheral blood lymphocytes of normal donors and patients with Down's syndrome. Genetika1968;4:51-63.

Sasaki MS

Tonomura A.

Matsubawa S.

: Chromosome constitution and its bearing on the chromosomal radiosensitivity in man. Mutat Res1970;10:617-633.

Shafik HM

Au WW

Legator MS

: Chromosomal radiosensitivity of Down syndrome lymphocytes at different stages of the cycle. Hum Genet1988;78:71-75.

10.

Otsuka F.

Tarone RE

Seguin LR

Robbins JH

: Hypersensitivity to ionizing radiation in cultured cells from Down syndrome patients. J Neurol Sci1985;9:103-112.

11.

Lavin MF

Bates P.

LeRoidevin P.

Chen PC

: Normal inhibition of DNA synthesis following γ-irradiation of radiosensitive cell lines from patients with Down's syndrome and Alzheimer's disease. Mutat Res1989;218:41-47.

12.

Huang CC

Banerjee A.

Tan JC

Hou Y.

: Comparison of radiosensitivity between human hematopoietic cell lines derived from patients with Down's syndrome and normal persons. J Natl Cancer Inst1977;59:33-36.

13.

Leonard JC

Merz T.

: Chromosomal aberrations in irradiated Down's syndrome fibroblasts . Mutat Res1987;180:223-230.

14.

Weichsebaum RR

Nove J.

Little J.

: X-ray sensitivity of fifty-three human diploid fibroblast strains from patients with characterized genetic disorders. Cancer Res1980;40:920-925.

15.

Yotti LP

Glover TN

Trosko JE

Segal DJ

: Comparative study of x-ray and UV induced cytotoxicity, DNA repair and mutagenesis in Down's syndrome and normal fibroblasts. Pediatr Res1980;14:88-92.

16.

Waghray M.

Al-Sedairy S.

Ozand PT

Hannan MA

: Cytogenetic characterization of ataxia telangiectasia (AT) heterozygotes using lymphoblastoid cell lines and chronic γ-irradiation. Hum Genet1990;84:532-534.

17.

Hannan MA

Blocher D.

Sigut D.

Waghray M.

: DNA double-strand breaks in fibroblast cell lines, from non-Hodgkin's lymphoma patients, showing increased sensitivity to chronic gamma irradiation . Cancer Lett1991 ;57:137-143.

18.

Harnden DG

Klinger HP

(eds): ISCN: An International System for Human Cytogenetic Nomenclature. Basel, Karger, 1985.

19.

Robbins JH

Brumback RA

Polinsky RJ

, et al: Hypersensitivity to DNA damaging agents in abiotrophies: A new explanation for degeneration of neurons, photoreceptors and muscle in Alzheimer, Parkinson and Huntington diseases, retinitis pigmentosa and Duchenne muscular dystrophy, in

Woodland AD

Blackett AD

Hollaender A

(eds): Molecular Biology of Aging. New York, Plenum Press, 1985, pp 315-354.

20.

Arlett CF

Harcourt SA

: Survey of radiosensitivity in a variety of human cell strains. Cancer Res1980;40:926-932.

21.

Paterson MC

Bech-Hansen NT

Smith PJ

: Heritable radiosensitive and DNA repair deficient disorders in man , in

Seeberg E

Kleppe K

(eds): Chromosome Damage and Repair. New York, Plenum Press, 1981, pp 335-354.

22.

Higurashi M.

Conen PE

: In vitro chromosomal radiosensitivity in patients and carriers with abnormal non-Down's syndrome karyotypes. Pediatr Res1972;6:514-520.

23.

Gentner NE

Morrison DP

Myers DK

: Impact on radiogenic-cancer risk of persons exhibiting abnormal sensitivity to ionizing radiation. Health Phys1988;55:415-425.

24.

Hannan MA

Smith BP

Sigut D.

Sackey K.

: Radiosensitivity of fibroblasts obtained from a cafe-au-lait spot and normal appearing skin of a patient with neurofibromatosis (NF-6). Cancer Genet Cytogenet1990;47:191-196.

25.

Hannan MA

Greer W.

Smith BP

, et al: Skin fibroblast cell lines derived from non-Hodgkin's lymphoma (NHL) patients show increased sensitivity to chronic gamma irradiation. Int J Cancer1991;47:261-266.