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

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