Relationship between DNA alkylation and specific-locus mutation induction by N-methyl- and N-ethyl-N-nitrosourea in cultured Chinese hamster ovary cells (CHO/HGPRT system) |
| |
Authors: | H-W Thielmann CH Schr?der JP ONeill PA Brimer AW Hsie |
| |
Institution: | 1. Deutsches Krebsforschungszentrum, Institut für Biochemie Heidelberg, Im Neuenheimer Feld 280, F.R.G.;2. Deutsches Krebsforschungszentrum, Institut für Virusforschung, 6900 Heidelberg, Im Neuenheimer Feld 280, F.R.G.;3. Biology Division, Oak Ridgs National Laboratory, Oak Ridge, TN 37830 U.S.A. |
| |
Abstract: | Chinese hamster ovary (CHO) cells in culture were utilized to determine the cytotoxicity, specific-locus mutation induction, and DNA alkylation which result from treatment of the cells with a range of concentrations of N-methyl-N-nitrosourea (MNU) or N-ethyl-N-nitrosourea (ENU). With 3H]MNU over the concentration range 0.43--13.7 mM, methylation of DNA was found to increase linearly, with a mean value of 56.7 pmol residue per mumol nucleoside per mM. With 1-3H]ENU over the concentration range 1.7--26.8 mM, ethylation was linear, with a mean value of 3.8 pmol residue per mumol nucleotide per mM. Mutation induction at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus was quantified by determination of the frequency of resistance to 6-thioguanine under stringently-defined selection conditions. The mutation frequency increased linearly with MNU or ENU concentration (0.01--2.0 mM); mean values were 2800 and 840 mutants per 10(6) clonable cells per mM, respectively. At equal levels of DNA alkylation, ENU was found to be approx. 4.5 times as mutagenic as MNU. |
| |
Keywords: | CHO cells DMSO dimethylsulfoxide EDTA ethylenediaminetetraacetic acid ENU HGPRT hypoxanthine-guanine phosphoribosyl transferase MNU TG 6-thioguanine (2-amino 6-mercaptopurine) TG resistant |
本文献已被 ScienceDirect 等数据库收录! |
|