scholarly journals The induction of ouabain-resistant mutants by N-methyl-N′-nitro-N-nitrosoguanidine in Chinese hamster cells

1974 ◽  
Vol 24 (3) ◽  
pp. 311-314 ◽  
Author(s):  
Peter J. Davies ◽  
Jim Parry
Keyword(s):  
Chinese Hamster ◽  
Steroid Compound ◽  
Chinese Hamster Cells ◽  
Mutagen Treatment ◽  
Induced Mutants ◽  
Resistant Mutants ◽  
Mnng Treatment ◽  
Expression Time

SUMMARYClones of V79 Chinese hamster cells resistant to the steroid compound ouabain have been induced by mutagen treatment with MNNG (= N-methyl-N′-nitro-N-nitrosoguanidine). The frequency of resistant colonies was increased from spontaneous value of 2 × 10−6 to a frequency of 1·2 × 10−3 with MNNG treatment.The highest number of induced mutants appeared when an expression time pf 40 h was allowed between MNNG treatment and addition of ouabain.

Specific induction of ACNU-resistance in V79 Chinese hamster cells and C6 rat glioma cells

1987 ◽  
Vol 67 (4) ◽  
pp. 553-557 ◽  
Author(s):  
Yukio Horie ◽  
Kenji Arai ◽  
Shunro Endoh ◽  
Toshio Kuroki ◽  
Akira Takaku
Keyword(s):  
Alkylating Agents ◽  
Lethal Dose ◽  
Chinese Hamster ◽  
Glioma Cells ◽  
Specific Effect ◽  
Cellular Level ◽  
Content Type ◽  
Chinese Hamster Cells ◽  
Rat Glioma ◽  
Resistant Mutants

✓ The antitumor compound ACNU (1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride) is widely used for treatment of malignant brain tumors. The authors have investigated the mechanism of acquisition of ACNU resistance at the cellular level by isolating ACNU-resistant mutants from V79 Chinese hamster cells and C6 rat glioma cells after treatment of the cells with ACNU or other alkylating agents. In V79 Chinese hamster cells, ACNU at 1 to 4 µg/ml caused dose-dependent induction of drug-resistant mutants to ACNU (10 µg/ml) and 8-azaguanine (20 µg/ml), but not to ouabain (1 mM). Values for the mean lethal dose of ACNU-resistant mutants were 2.4 to 17.2 times those of the parent V79 cells. The ACNU-resistant phenotype was stable during an observation period of 13 weeks. The ACNU seemed to have a specific effect in inducing ACNU-resistant mutations, because no ACNU-resistant mutations were induced by treatment of the cells with other known mutagens, such as N-methyl-N′-nitro-N-nitrosoguanidine, methylmethanesulfonate, and ethylmethanesulfonate. The C6 rat glioma cells also showed a significant mutagenic response to ACNU, producing ACNU- and 5-fluorouracil-resistant mutants. The present results have the important therapeutic and mechanistic implication that ACNU is a potent mutagen and induces mutants that are resistant to ACNU and to other drugs.

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