Isolation of two chloroethylnitrosourea-sensitive Chinese hamster cell lines
1-[(4-Amino-2-methylpyrimidin-5-yl)methyl]-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU), a cancer chemotherapeutic bifunctional alkylating agent, causes chloroethylation of DNA and subsequent DNA strand cross-linking through an ethylene bridge. We isolated and characterized two ACNU-sensiti...
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Published in | Cancer research (Chicago, Ill.) Vol. 51; no. 1; pp. 195 - 198 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Philadelphia, PA
American Association for Cancer Research
1991
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Abstract | 1-[(4-Amino-2-methylpyrimidin-5-yl)methyl]-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU), a cancer chemotherapeutic bifunctional alkylating agent, causes chloroethylation of DNA and subsequent DNA strand cross-linking through an ethylene bridge. We isolated and characterized two ACNU-sensitive mutants from mutagenized Chinese hamster ovary cells and found them to be new drug-sensitive recessive Chinese hamster mutants. Both mutants were sensitive to various monofunctional alkylating agents in a way similar to that of the parental cell lines CHO9. One mutant (UVS1) was cross-sensitive to UV and complemented the UV sensitivity of all Chinese hamster cell lines of 7 established complementation groups. Since UV-induced unscheduled DNA synthesis was very low, a new locus related to excision repair is thought to be defective in this cell line. Another ACNU-sensitive mutant, CNU1, was slightly more sensitive to UV than the parent cell line. CNU1 was cross-sensitive to 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and slightly more sensitive to mitomycin C. No increased accumulation of ACNU and a low level of UV-induced unscheduled DNA synthesis in this cell as compared with the parental cell line suggest that there is abnormality in a repair response of this mutant cell to some types of DNA cross-links. |
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AbstractList | 1-[(4-Amino-2-methylpyrimidin-5-yl)methyl]-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU), a cancer chemotherapeutic bifunctional alkylating agent, causes chloroethylation of DNA and subsequent DNA strand cross-linking through an ethylene bridge. We isolated and characterized two ACNU-sensitive mutants from mutagenized Chinese hamster ovary cells and found them to be new drug-sensitive recessive Chinese hamster mutants. Both mutants were sensitive to various monofunctional alkylating agents in a way similar to that of the parental cell lines CHO9. One mutant (UVS1) was cross-sensitive to UV and complemented the UV sensitivity of all Chinese hamster cell lines of 7 established complementation groups. Since UV-induced unscheduled DNA synthesis was very low, a new locus related to excision repair is thought to be defective in this cell line. Another ACNU-sensitive mutant, CNU1, was slightly more sensitive to UV than the parent cell line. CNU1 was cross-sensitive to 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and slightly more sensitive to mitomycin C. No increased accumulation of ACNU and a low level of UV-induced unscheduled DNA synthesis in this cell as compared with the parental cell line suggest that there is abnormality in a repair response of this mutant cell to some types of DNA cross-links. 1-((4-Amino-2-methylpyrimidin-5-yl)methyl)-3-(2-chloroethyl)-3-nit rosourea hydrochloride (ACNU), a cancer chemotherapeutic bifunctional alkylating agent, causes chloroethylation of DNA and subsequent DNA strand cross-linking through an ethylene bridge. We isolated and characterized two ACNU-sensitive mutants from mutagenized Chinese hamster ovary cells and found them to be new drug-sensitive recessive Chinese hamster mutants. Both mutants were sensitive to various monofunctional alkylating agents in a way similar to that of the parental cell lines CHO9. One mutant (UVS1) was cross-sensitive to UV and complemented the UV sensitivity of all Chinese hamster cell lines of 7 established complementation groups. Since UV-induced unscheduled DNA synthesis was very low, a new locus related to excision repair is thought to be defective in this cell line. Another ACNU-sensitive mutant, CNU1, was slightly more sensitive to UV than the parent cell line. CNU1 was cross-sensitive to 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and slightly more sensitive to mitomycin C. No increased accumulation of ACNU and a low level of UV-induced unscheduled DNA synthesis in this cell as compared with the parental cell line suggest that there is abnormality in a repair response of this mutant cell to some types of DNA cross-links. |
Author | YASUI, A OIKAWA, A TOHDA, H HATA, H NUMATA, M |
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Keywords | Cell culture Nitrosoureas Rodentia Crosslinking In vitro CHO cell line Ovary Vertebrata Alkylating agent Sensitivity Mammalia Sensitivity resistance Investigation method Animal DNA Female genital system Lesion Repair Nucleic acid Hamster |
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SubjectTerms | 560120 - Radiation Effects on Biochemicals, Cells, & Tissue Culture 560300 - Chemicals Metabolism & Toxicology ALKYLATING AGENTS ANIMAL CELLS Animals Antineoplastic agents Biological and medical sciences BIOLOGICAL EFFECTS BIOLOGICAL RECOVERY BIOLOGICAL REPAIR Cell Line Cell Survival - drug effects CHEMICAL REACTIONS CHO CELLS Cisplatin - pharmacology Cricetinae Cricetulus CROSS-LINKING DNA Damage DNA REPAIR DNA REPLICATION Dose-Response Relationship, Drug DOSE-RESPONSE RELATIONSHIPS ELECTROMAGNETIC RADIATION EXCISION REPAIR General aspects Genetic Complementation Test GENETIC EFFECTS In Vitro Techniques Medical sciences Mitomycin Mitomycins - pharmacology Nimustine - metabolism Nimustine - pharmacology NITROSO COMPOUNDS NITROSOUREAS NUCLEIC ACID REPLICATION ORGANIC COMPOUNDS ORGANIC NITROGEN COMPOUNDS Pharmacology. Drug treatments POLYMERIZATION RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT RADIATIONS RECOVERY REPAIR SENSITIVITY ULTRAVIOLET RADIATION Ultraviolet Rays X-Rays |
Title | Isolation of two chloroethylnitrosourea-sensitive Chinese hamster cell lines |
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