Summary
The effect of treatment with 8-methoxypsoralen (8-MOP) plus near-UV radiation (UVA) or with X-rays on the rate of DNA semi-conservative synthesis of fibroblasts from 10 Fanconi anemia (FA), two heterozygous, and three normal cell lines was studied. Following treatments with either X-rays or low doses of 8-MOP plus UVA leading to a majority of monoadducts over cross-links per genome, the FA and hetcrozygous cell lines were indistinguishable from normals: the transient inhibition of semi-conservative DNA synthesis was followed by the recovery of a nomral rate of synthesis. In contrast treatment with higher (but not saturating) doses of 8-MOP plus UVA allowed us to distinguish two classes among the FA cell lines. One class demonstrated a pattern of recovery similar to that of heterozygous and normal cell lines. This indicates that in such cell lines, the predominant lesion in this condition, the cross-links, do not arrest DNA synthesis and are likely to be normally repaired. Another class of FA cell lines did not show a recovery of a normal rate of DNA synthesis even after prolonged post-treatment incubation and although the proportion of cells in S phase was similar to that of the strains of the first category. This indicates that in such cell lines the repair of cross-links is inhibited at some step which is not necessarily the incision one.
Similar content being viewed by others
References
Ahmed FE, Setlow RB (1979) Saturation of DNA repair in mammalian cells. Photochem Photobiol 29:983–989
Auerbach AD, Wolman SR (1976) Susceptibility of Fanconi's anemia fibroblasts to chromsome damage by carcinogens. Nature 261:494–496
Auerbach AD, Wolman SR (1978) Carcinogen-induced chromosome breakage in Fanconi anemia heterozygous cells. Nature 271:69–71
Baden HP, Parrington JM, Delhanty JD, Pathak MA (1972) DNA synthesis in normal and xeroderma pigmentosum fibroblasts following treatment with 8-methoxypsoralen and long-wave ultraviolet light. Biochim Biophys Acta 262:247–255
Berger R, Bernheim A, Coniat ML, Vecchione D, Schaison G (1980) Nitrogen mustard-induced chromosome breakage. A tool to Fanconi's anemia diagnosis. Cancer Genet Cytogenet 2:269–274
Bigelow SB, Rary JM, Bender MA (1979) G2 chromosomal radiosensitivity in Fanconi's anemia Mutat Res 63:189–199
Cervenka J, Arthur D, Yasis C (1981) Mitomycin C test for diagnosis differentiation of idiopathic aplastic anemia and Fanconi's anemia. Pediatrics 67:119–127
Cohen MM, Simpson SJ, Honig GR, Maurer HS, Niclas JW, Martin AO (1982) The identification of Fanconi's anemia genotypes by clastogenic stress. Am J Hum Genet 34:794–810
Coquerelle TM, Weibezahn KF (1981) Rejoining of DNA doublestrand breaks in human fibroblasts and its impairment in one ataxia telangiectasia and two Fanconi strains. J Supramol Struc Cell Biochem 17:369–376
Dean SW, Fox M (1984) DNA repair, DNA synthesis and cell cycle delay in human lymphoblastoid cells differentially sensitive to cytotoxic effects of nitrogen mustard. Mutat Res 132:63–72
De Wit J, Jaspers NGJ, Bootsma D (1981) The rate of DNA synthesis in normal human and ataxia telangiectasia after exposure to X-irradiation. Mutat Res 80:221–226
Diatloff C, Macieira-Coellho A (1979) Effect of low dose rate irradiation on the division potential of cells in vitro. V: Human skin fibroblasts from donors with high risk of cancer. JNCI 63:55–59
Dutreix J, Gluckman E (1983) Skin test ofradiosensitivity. Application to Fanconi's anemia. J Eur Radiother 4:3–8
Dutrillaux B, Aurias A, Dutrillaux AM, Buriot D, Prieur M (1982) The cell cycle of lymphocytes in Fanconi's anemia. Hum Genet 62:327–332
Elmore E, Swift M (1976) Growth of cultured cells from patients with Fanconi's anemia. J Cell Physiol 87:229–239
Fanconi G (1976) Familial constitutional panmyelopathy, Fanconi's anemia (FA). I. Clinical aspects. Semin Hematol 4:233–240
Fornace AJ, Little JB, Weichselbaum RR (1979) DNA repair in a Fanconi's anemia fibroblast cell strain. Biochim Biophys Acta 561:99–109
Fujiwara Y (1982) Defective repair of mitomycin C cross-links in Fanconi's anemia and loss in confluent normal human and xeroderma pigmentosum cells. Biochim Biophys Acta 699:217–225
Fujiwara Y, Tatsumi M, Sasaki MS (1977) Cross-link repair in human cells and its possible defect in Fanconi's anemia cells. J Mol Biol 113:635–649
Hand R (1977) Human DNA replication: Fiber autoradiographic analysis of diploid cells from normal adults and from Faconi's anemia and ataxia telangiectasia. Hum Genet 37:55–64
Houldsworth J, Lavin MF (1980) Effect of ionizing radiation on DNA synthesis in ataxia telangiectasia. Nucleic Acids Res 8:3709–3720
Hyodo M, Fujija H, Susuki K, Yoshino K, Matsuo I, Ohkido M (1982) DNA replication and cell-cycle progression of cultured mouse FM 3 A cells after treatment with 8-methoxypsoralen plus near-UV irradiation. Mutat Res 94:199–211
Ishida R, Buchwald M (1982) Susceptibility of Fanconi's anemia lymphoblasts to DNA-cross-linking and alkylating agents. Cancer Res 42:4000–4006
Kaiser TN, Lojewski A, Dougherty C, Juergens L, Sahar E, Latt SA (1982) Flow cytometric characterization of the response of Fanconi's anemia cells to mitomycin C treatment. Cytometry 2:291–297
Kaye J, Smith CA, Hanawalt PC (1980). DNA repair in human cells containing photoadducts of 8-methoxypsoralen or angelicin. Cancer Res 40:696–702
Kwee ML, Poll EHA, Van de Kamp JJP, De Koning H, Erikson AW, Joenje H (1983) Unusual response to bifunctional alkylating agents in a case of Fanconi anemia. Hum Genet 64:384–387
Latt SA, Stetler E, Jengens LA, Buchanan AR, Gerald PS (1975) Induction by alkylating agents of sister chromatid exchanges and chromatid breaks in Fanconi's anemia. Proc Natl Acad Sci USA 72:4066–4070
Lehman AR, Kirk-Bell S, Mayne L (1979) Abnormal kinetics of DNA synthesis in ultraviolet irradiated cells from patients with Cockayne's syndrome. Cancer Res 39:4237–4241
Marx MP, Smith S, Heyns A du P, Van Tonder IZ (1983) Fanconi's anemia: A cytogenetic study on lymphocyte and bone marrow cultures utilizing 1,2:3,4 diepoxybutane. Cancer Genet Cytogenet 9:51–60
Moustacchi E, Ehmann UK, Friedberg EC (1979) Defective recovery of semi-conservative DNA synthesis in xeroderma pigmentosum cells following split-dose ultraviolet irradiation. Mutat Res 62:159–171
Painter RB (1977) Rapid test to detect agents that damage human DNA. Nature 265:650–651
Painter RB (1981) Radioresistant DNA synthesis: An intrinsic feature of ataxia telangiectasia. Mutat Res 84:183–190
Poll EHA (1984) Fanconi's anemia: Sensitivity of its cells to DNA-crosslinking agents. PhD, Vrije Universiteit te Amsterdam, Amsterdam (Holland)
Porfirio B, Dallapicola B, Alimana G, Gandini E (1983) Failure of diepoxybutane to enhance sister chromatid exchange levels in Fanconi's anemia patients and heterozygotes. Hum Genet 63:117–120
Rainbow AJ, Howes M (1977) Defective repair of ultraviolet and gamma-ray damaged DNA in Fanconi's anemia. Int J Radiat Biol 31:191–195
Remsen JF, Cerutti PA (1976) Deficiency of gamma-ray excision repair in skin fibroblasts from patients with Fanconi's anemia. Proc Natl Acad Sci USA 73:2419–2423
Rudé JM, Friedberg EC (1977) Semi-conservative deoxyribonucleic acid synthesis in unirradiated and ultraviolet-irradiated xeroderma pigmentosum and normal human skin fibroblasts. Mutat Res 42:433–442
Sasaki MS, Tonomura A (1973) A high susceptibility of Fanconi's anemia to chromosome breakage by DNA-crosslinking agents. Cancer Res 33:1829–1836
Schroeder TM (1982) Genetically determined chromosome instability syndromes. Cytogenet Cell Genet 13:119–132
Sognier MA, Hittelman WN (1983) Loss of repairability of DNA interstrand cross-links in Fanconi's anemia cells with culture age. Mutat Res 108:383–393
Song PS, Tapley KJ (1979) Photochemistry and photobiology of psoralens. Photochem Photobiol 29:1177–1197
Trosko JE, Isoun M (1971) Photosensitizing effect of trisoralen on DNA synthesis in human cells grown in vitro. Int J Radiat Biol 19:87–92
Voss R, Kohn G, Shaham M, Benzur Z, Arnon J, Ornoy A, Yaffe H, Golbus M, Auerbach AD (1981) Prenatal diagnosis of Fanconi anemia. Clin Genet 20:185–190
Watanabe I (1974) Radiation effects on DNA chain growth in mammalian cells. Radiat Res 58:541–556
Weksberg R, Buchwald M, Sargent P, Thompson MW, Siminovitch L (1979) Specific cellular defects in patients with Fanconi's anemia. J Cell Physiol 101:311–324
Wunder E, Fleischer-Reischmann B (1983) Response of lymphocytes from Fanconi's anemia patients and their heterozygous relatives to 8-methoxypsoralen in a cloning survival test system. Hum Genet 64:167–172
Zamansky GB, Little JB (1982) Survival of 60Co-irradiated-herpes simplex virus in 15 human diploïd fibroblast cell strains. Mutat Res 94:245–255
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Moustacchi, E., Diatloff-Zito, C. DNA semi-conservative synthesis in normal and Fanconi anemia fibroblasts following treatment with 8-methoxypsoralen and near ultraviolet light or with X-rays. Hum Genet 70, 236–242 (1985). https://doi.org/10.1007/BF00273448
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00273448