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. 1977 Jul 1;74(1):274–286. doi: 10.1083/jcb.74.1.274

Developmental decline in DNA repair in neural retina cells of chick embryos: persistent deficiency of repair competence in a cell line derived from late

P Karran, A Moscona, B Strauss
PMCID: PMC2109876  PMID: 559680

Abstract

Neural retinas of 6-day-old chick embryos synthesize DNA and are able to carry out DNA excision repair. However, in contrast to the situation in human cells, the maximum rate of repair induced by N-acetoxy acetylaminofluorene (AAAF) is no greater than that induced by methyl methanesulfonate (MMS). With advancing differentiation of the retina in the embryo, cell multiplication and DNA synthesis decline and cease, and concurrently the cells lose the ability to carry out DNA excision repair. Thus, in 15-16-day embryos, in which the level of DNA synthesis is very low, DNA repair is barely detectable. If retinas from 14-day embryos are dissociated with trypsin and the cell suspension is plated in growth- promoting medium, DNA synthesis is reinitiated; however, in these cultures there is no detectable repair of MMS-induced damage, and only low levels of repair are observed after treatment with AAAF. A cell line was produced, by repeated passaging of these cultures, in which the cell population reached a steady state of DNA replication. However, the cell population remained deficient in the ability to repair MMS-induced damage. This cell line most likely predominantly comprises cells of retino-glial origin. Possible correlations between deficiency in DNA repair mechanisms in replicating cells and carcinogenesis in neural tissues are discussed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ALTMAN J. Autoradiographic study of degenerative and regenerative proliferation of neuroglia cells with tritiated thymidine. Exp Neurol. 1962 Apr;5:302–318. doi: 10.1016/0014-4886(62)90040-7. [DOI] [PubMed] [Google Scholar]
  2. Bosch D. A., Gerrits P. O., Ebels E. J. The cytotoxic effect of ethylnitrosourea and methylnitrosourea on the nervous system of the rat at different stages of development. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1972;77(4):308–318. doi: 10.1007/BF00283974. [DOI] [PubMed] [Google Scholar]
  3. Byfield J. E., Lee Y. C., Klisak I., Finklestein J. Z. Effect of differentiation on the repair of DNA single strand breaks in neuroblastoma cells. Biochem Biophys Res Commun. 1975 Apr 7;63(3):730–735. doi: 10.1016/s0006-291x(75)80444-x. [DOI] [PubMed] [Google Scholar]
  4. Coyle M., McMahon M., Strauss B. Failure of alkylated HEp.2 cells to replicate newly synthesized DNA. Mutat Res. 1971 Aug;12(4):427–440. doi: 10.1016/0027-5107(71)90093-5. [DOI] [PubMed] [Google Scholar]
  5. Craig R. K., Keir H. M. Deoxyribonucleic acid polymerases of BHK-21/C13 cells. Partial purification and characterization of the enzymes. Biochem J. 1975 Feb;145(2):215–224. doi: 10.1042/bj1450215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goth R., Rajewsky M. F. Persistence of O6-ethylguanine in rat-brain DNA: correlation with nervous system-specific carcinogenesis by ethylnitrosourea. Proc Natl Acad Sci U S A. 1974 Mar;71(3):639–643. doi: 10.1073/pnas.71.3.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hahn G. M., King D., Yang S. J. Quantitative changes in unscheduled DNA synthesis in rat muscle cells after differentiation. Nat New Biol. 1971 Apr 21;230(16):242–244. doi: 10.1038/newbio230242a0. [DOI] [PubMed] [Google Scholar]
  8. Kaplowitz P. B., Moscona A. A. Lectin-mediated stimulation of DNA synthesis in cultures of embryonic neural retina cells. Exp Cell Res. 1976 Jun;100(1):177–189. doi: 10.1016/0014-4827(76)90340-2. [DOI] [PubMed] [Google Scholar]
  9. Kaplowitz P. B., Moscona A. A. Stimulation of DNA synthesis by ouabain and concanavalin A in cultures of embryonic neural retina cells. Cell Differ. 1976 Jul;5(2):109–119. doi: 10.1016/0045-6039(76)90004-x. [DOI] [PubMed] [Google Scholar]
  10. Karran P., Ormerod M. G. Is the ability to repair damage to DNA related to the proliferative capacity of a cell? The rejoining of X-ray-produced strand breaks. Biochim Biophys Acta. 1973 Feb 23;299(1):54–64. doi: 10.1016/0005-2787(73)90397-3. [DOI] [PubMed] [Google Scholar]
  11. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  12. Loeb L. A. Purification and properties of deoxyribonucleic acid polymerase from nuclei of sea urchin embryos. J Biol Chem. 1969 Apr 10;244(7):1672–1681. [PubMed] [Google Scholar]
  13. Loveless A. Possible relevance of O-6 alkylation of deoxyguanosine to the mutagenicity and carcinogenicity of nitrosamines and nitrosamides. Nature. 1969 Jul 12;223(5202):206–207. doi: 10.1038/223206a0. [DOI] [PubMed] [Google Scholar]
  14. Painter R. B., Young B. R. Repair replication in mammalian cells after x-irradiation. Mutat Res. 1972 Feb;14(2):225–235. doi: 10.1016/0027-5107(72)90049-8. [DOI] [PubMed] [Google Scholar]
  15. Pegoraro L., Bernengo M. G. Thymidine kinase, deoxycytidine kinase and deoxycytidylate deaminase activities in phytohaemagglutinin stimulated human lymphocytes. Exp Cell Res. 1971 Oct;68(2):283–290. doi: 10.1016/0014-4827(71)90152-2. [DOI] [PubMed] [Google Scholar]
  16. Rabinowitz Y., McCluskey I. S., Wong P., Wilhite B. A. DNA polymerase activity of cultured normal and leukemic lymphocytes. Response to phytohemagglutinin. Exp Cell Res. 1969 Oct;57(2):257–262. doi: 10.1016/0014-4827(69)90149-9. [DOI] [PubMed] [Google Scholar]
  17. Regan J. D., Setlow R. B. Two forms of repair in the DNA of human cells damaged by chemical carcinogens and mutagens. Cancer Res. 1974 Dec;34(12):3318–3325. [PubMed] [Google Scholar]
  18. Scudiero D., Henderson E., Norin A., Strauss B. The measurement of chemically-induced DNA repair synthesis in human cells by BND-cellulose chromatography. Mutat Res. 1975 Sep;29(3):473–488. doi: 10.1016/0027-5107(75)90066-4. [DOI] [PubMed] [Google Scholar]
  19. Scudiero D., Norin A., Karran P., Strauss B. DNA excision-repair deficiency of human peripheral blood lymphocytes treated with chemical carcinogens. Cancer Res. 1976 Apr;36(4):1397–1403. [PubMed] [Google Scholar]
  20. Seeds N. W., Gilman A. G., Amano T., Nirenberg M. W. Regulation of axon formation by clonal lines of a neural tumor. Proc Natl Acad Sci U S A. 1970 May;66(1):160–167. doi: 10.1073/pnas.66.1.160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Stockdale F. E. DNA synthesis in differentiating skeletal muscle cells: initiation by ultraviolet light. Science. 1971 Mar 19;171(3976):1145–1147. doi: 10.1126/science.171.3976.1145. [DOI] [PubMed] [Google Scholar]
  22. Swenberg J. A., Koestner A., Wechsler W., Denlinger R. H. Quantitative aspects of transplacental tumor induction with ethylnitrosourea in rats. Cancer Res. 1972 Dec;32(12):2656–2660. [PubMed] [Google Scholar]
  23. VARON S. S., RAIBORN C. W., Jr, SETO T., POMERAT C. M. A cell line from trypsinized adult rabbit brain tissue. Z Zellforsch Mikrosk Anat. 1963;59:35–46. doi: 10.1007/BF00321006. [DOI] [PubMed] [Google Scholar]

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