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DNA Repair Mechanisms and Their Biological Implications in Mammalian Cells pp 83–99Cite as

The Mer Minus Phenotype, Patient Response to Nitrosoureas, and Protooncogene Activation in Human Glioblastomas

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Part of the book series: NATO ASI Series ((NSSA,volume 182))

Abstract

It is about 10 years since the identification of the first Mer line, A172 (Day and Ziolkowski, 1979), a human astrocytoma line produced by Giard, et al.(1973). To review, Mer lines are human cell lines defined by their relative inability to support the growth of adenovirus 5 that has been treated with N-methyl-N -nitro-N-nitrosoguanidine (MNNG) prior to infection of cell monolayers (Day, et al., 1980a,b). Such lines lack, without exception, the ability to repair m6 Gua produced in their DNA by certain methylating agents (Day, et al., 1980a; Day, et al., 1984), and are thus Mex- by the definition of Sklar and Strauss (1981). Mer- strains produced from human tumors are highly sensitive with respect to Mer+ cells as assessed by several endpoints to agents that react with the O6 of guanine: sister chromatid exchange (Day, et al., 1980a), mutation induction (Baker, et al., 1979, 1980, Domoradski, et al., 1984), cell killing by MNNG or nitrosoureas (Day, et al., 1980a,b; Erickson, 1980a,b; Scudiero, et al., 1984 a,b; Gibson, et al., 1986). The results obtained in cell culture are clear-cut; for example, with MNNG as the damaging agent, the inactivation slopes of survival curves of Mer- cells are up to 50 fold steeper than are those of Mer+ cells (Scudiero, et al., 1984a). Several groups have inserted parts or all of the E. coli ada gene into Mex- cells and have provided evidence that such differential sensitivity is likely due to differential repair of m6Gua (Brennand and Margison, 1986, Ishizaki, et al., 1986; Kataoka, et al., 1986; Samson, et al., 1986; Fox, et al., 1987), a point which has been discussed previously, and for which there is substantial evidence (Day, et al., 1987). No matter how persuading the cell culture evidence, there is little evidence to demonstrate that Mer- cells occur in tumors; i.e., that some fraction of human tumors is composed of Mer- cells.

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Authors and Affiliations

  1. Department of Medicine, Molecular Genetics and Carcinogenesis Laboratory, Canada

    Rufus S. Day III, Junji Miyakoshi & Kelly Dobler

  2. Department of Radiation Oncology, Radiobiology Laboratory, Canada

    Joan Allalunis-Turner

  3. Division of Neurosurgery, Faculty of Medicine, University of Alberta, Edmonton, Alberta, T6G 2G3, Canada

    John D. S. McKean, Kenneth Petruk, Peter B. R. Allen, Keith N. Aronyk & Bryce Weir

  4. Department of Radiation Oncology, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, T6G 1Z2, Canada

    Debbie Huyser-Wierenga, Dorcas Fulton & Raul C. Urtasun

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  1. Rufus S. Day III
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Editors and Affiliations

  1. New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA

    Muriel W. Lambert

  2. Institut Gustave Roussy, Villejuif, France

    Jacques Laval

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© 1989 Plenum Press, New York

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Day, R.S. et al. (1989). The Mer Minus Phenotype, Patient Response to Nitrosoureas, and Protooncogene Activation in Human Glioblastomas. In: Lambert, M.W., Laval, J. (eds) DNA Repair Mechanisms and Their Biological Implications in Mammalian Cells. NATO ASI Series, vol 182. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-1327-4_8

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  • DOI: https://doi.org/10.1007/978-1-4684-1327-4_8

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