Developmental Decline in DNA Repair in Neural Retina Cells of Chick Embryos: Persistent Deficiency of Repair Competence in a Cell Line Derived from Late Embryos

• Published in: The Journal of cell biology 1977-07, Vol.74 (1), p.274-286
• Main Authors: Karran, Peter, Moscona, Aron, Strauss, Bernard
• Format: Article
• Language: English
• Subjects: Acetoxyacetylaminofluorene - pharmacology; Animals; Cell culture techniques; Cell Differentiation; Cell Division; Cell Line; Cell lines; Cells; Chick Embryo; Cultured cells; DNA; DNA - biosynthesis; DNA Repair; DNA-Directed DNA Polymerase - metabolism; Embryonic cells; Kinetics; Methyl Methanesulfonate - pharmacology; Neuroglia; Neurons; Retina; Retina - cytology; Retina - embryology; Thymidine Kinase - metabolism; Trypsin - pharmacology
• ISSN: 0021-9525
• DOI: 10.1083/jcb.74.1.274

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.