Evidence for spontaneous conversion of Mex- to Mex+ in human lymphoblastoid cells.
A series of human lymphoblastoid cell lines (LCLs) called Mex- were defined by Sklar and Strauss on the basis of their inability to remove O6-methylguanine from DNA. Instability of Mex- has previously been shown as a population phenotype of LCLs. We examined whether Mex- as a cellular phenotype is spontaneously convertible or not. At the population doubling number (PDN) 23 after recloning, two out of 15 independent subcultures derived from a Mex- LCL, AT1-1, were found to contain a small fraction of Mex+ cells after treatment with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). Three Mex+ subclones were identified without exposure to ACNU among 486 subclones from replica plating of an expanded Mex- clone (PDN30). The rate of spontaneous conversion was estimated to be in the range of 10(-8)-10(-7) per cell per generation by the fluctuation analyses on two Mex- subclones. These results strongly support the hypothesis that Mex- as a cellular phenotype is spontaneously convertible to Mex+.
Arita
I
I
Department of Molecular Oncology, Faculty of Medicine, Kyoto University, Japan.
Fujimori
A
A
Takebe
H
H
Tatsumi
K
K
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D005785:Gene Conversion; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007621:Karyotyping; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D015376:Nimustine / Q000494:pharmacology; D019853:O(6)-Methylguanine-DNA Methyltransferase; D010641:Phenotype
D015376:Nimustine; D006147:Guanine; C008449:O-(6)-methylguanine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase