Summary
The effects of cytidine and cytidine analogs were studied inDrosophila embryonic cell cultures and two wild-type established cell lines, Oregon-R and Schneider line 2. Primary embryonic cultures have been shown to be an excellent system for the study of embryonic development; a number of cell types undergo normal differentiation in vitro. Treatment of these cultures with putative teratogens resulted in an inhibition of muscle and/or neuron differentiation in our study. Treatment of these cells with cytidine and seven other analogs had no effect on neuron and muscle differentiation. The compound 5-azacytidine, when added to primary cell cultures, inhibited normal differentiation at subtoxic doses while inducing the production of three proteins that comigrate with the heat-shock proteins, hsp 23, 22a and 22b. 5-Azacytidine did not stimulate differentiation in Oregon-R or SchneiderDrosophila cell lines. The in vitro blockage of differentiation by 5-azacytidine suggests that it may act as a teratogen.
This is a preview of subscription content, log in via an institution to check access.
References
Ashburner M, Bonner J (1979) The induction of gene activity inDrosophila by heat shock. Cell 17:241–254
Bournias-Vardiabasis N, Teplitz RL (1982) The use ofDrosophila embryonic cell cultures as anin vitro teratogen assay. Teratogenesis. Carcinog Mutagen 2:333–341
Bournias-Vardiabasis N, Teplitz RL, Chernoff GF, Seecof RL (1983) Detection of teratogens in theDrosophila in vitro test: Assay of 100 chemicals. Teratology [in press]
Buzin C, Bournias-Vardiabasis N (1982) The induction of a subset of heat shock proteins by drugs that inhibit differentiation inDrosophila embryonic cell cultures. In: Schlesinger MJ, Ashburner M, Tisseres A (eds). Heat shock from bacteria to man. Cold Spring Harbor Laboratory, pp 387–394
Buzin C, Seecof RL (1981) Developmental modulation of protein synthesis inDrosophila primary embryonic cell cultures. Dev Genet 2:237–252
Constantinides PG, Jones PA, Gevers W (1977) Functional striated muscle cells from non-myoblast precursors following 5-Azacytidine treatment. Nature 267:364–366
Constantinides PG, Taylor SM, Jones PA (1978) Phenotypic conversion of cultured mouse embryo cells by Aza pyrimidine nucleosides. Dev Biol 66:57–71
Holiday R, Pugh JE (1975) DNA modification mechanisms and gene activity during development. Science 187:226–232
Jones PA, Taylor SM (1980) Cellular differentiation cytidine analogs, and DNA methylation. Cell 20:85–93
Mitchell HK, Moller G, Petersen NS, Lipps-Sarmiento L (1979) Specific protection from phenocopy induction by heat shock. Dev Genet 1:181–192
O'Farrell P (1975) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250:4007–4021
Perey DH (1975) Teratogenic effects of pyrimidine analogues 5-iododeoxyuridine and cytosine arabinoside in late fetal mice and rats. Teratology 11:103–118
Petersen NS, Riggs AD, Seecof RL (1977) A method for establishing cell lines fromDrosophila melanogaster embryos. In vitro 13:36–40
Rae PM, Steele RT (1979) Absence of cytosine methylation at C-C-G-G and G-C-G-C sites in the rDNA coding regions and intervening sequences ofDrosophila and the rDNA of other higher insects. Nuc Acids Res 6:2987–2995
Razin A, Riggs AD (1980) DNA methylation and gene function. Science 187:226–232
Reilly JG, Thomas CA, Sen A (1982) DNA methylation in mouse cells in culture. Biochim Biophys Acta 697:53–59
Riggs AD (1975) X inactivation, differentiation, and DNA methylation. Cytogenet Cell Genet 14:9–25
Schmahl N (1978) Different teratogenic efficacy to mouse fetal CNS of 5-Auacytidine in combination with X-irradiation depends on the sequence of successive application. Teratology 18:143
Schneider I (1972) Cell lines derived from late embryonic stages ofDrosophila melanogaster. J Embryol Exp Morphol 27:353–365
Seecof RL (1980) Preparation of cell cultures fromDrosophila melanogaster embryos. Tissue Cult Assoc Man 5:1019–1022
Seecof RL, Donady JJ (1972) Factors affectingDrosophila neuron and mytocyte differentiationin vitro. Mech Aging Dev 1:165–174
Seecof RL, Alleaume N, Teplitz RL, Gerson I (1971) Differentiation of neurons and myocytes in cell cultures made fromDrosophila gastrulae. Exp Cell Res 69:161–173
Shepard TH (1981) Catalog of teratogenic agents. Johns Hopkins Press, Baltimore
Shields G, Dubendorfer A, Sang JH (1975) Differentiationin vitro of larval cell types from early embryonic cells ofDrosophila melanogaster. J Embryol Exp Morphol 33:159–175
Singer J, Roberts-Ems J, Riggs AD (1979) Methylation of mouse liver DNA studies by means of the restriction enzymes MSP I and Hpa II. Science 203:1019–1021
Smith SS, Thomas CA (1981) The two-dimensional restriction analysis ofDrosophila DNAs: Males and females. Gene 13:395–408
Taylor SM, Jones PA (1979) Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine. Cell 17:771–779
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bournias-Vardiabasis, N., Buzin, C.H. & Reilly, J.G. The effect of 5-azacytidine and cytidine analogs onDrosophila melanogaster cells in culture. Wilhelm Roux' Archiv 192, 299–302 (1983). https://doi.org/10.1007/BF00848664
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00848664