Induction and expression of mutations at multiple drug-resistance marker loci in Chinese hamster ovary cells
Abstract
We observed quantitative and qualitative differences in the mutability and mutagen-specificity of various drug-resistance marker loci in Chinese hamster ovary (THO) cells, which suggest that mammalian gene loci may differ in their relative mutability by a given mutagenic agent. We have used the CHO-AT3-2 multiple-marker mutagenesis assay system to examine the dose-dependent induction and kinetics of expression of mutations at four well-characterized, drug-resistance marker loci, after treatment with chemical agents which produce various types of DNA damage. The CHO-AT3-2 subline allows simultaneous quantitation and direct comparison of induced mutation frequencies at the hgprt, oua (Na/sup +//K/sup +/ ATPase), aprt, and tk loci. The agents tested in this study included ethyl methanesulfonate, methyl methanesulfonate, mitomycin C, ICR-191, benzo(a)pyrene, and dimethylnitrosamine. The expression kinetics and optimal expression times for each drug-resistance marker were determined in dose-response experiments in which cells from mutagen-treated populations were plated at 1-2-day intervals over a period of 10 days following mutagenesis. Comparison of induced mutation frequencies for each drug-resistance marker after mutagen treatments yielding equivalent cell survivals (equitoxic doses resulting in relative cell survivals of 0.37) revealed locus-specific differences in the relative mutagenicities of the agents tested. These results indicate that the apparent mutagenicity of a particularmore »
- Authors:
- Publication Date:
- Research Org.:
- Univ. of Texas System Cancer Center, Smithville
- OSTI Identifier:
- 5518870
- DOE Contract Number:
- W-7405-ENG-48
- Resource Type:
- Journal Article
- Journal Name:
- Environ. Mutagen.; (United States)
- Additional Journal Information:
- Journal Volume: 5:2
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; BENZOPYRENE; MUTAGENESIS; EMS; METHYL METHANESULFONATE; MITOMYCIN; NITROSAMINES; ATP-ASE; BIOASSAY; BIOCHEMICAL REACTION KINETICS; CHO CELLS; DNA; DOSE-RESPONSE RELATIONSHIPS; GENES; GENETIC EFFECTS; GENETIC MAPPING; GENETICALLY SIGNIFICANT DOSE; MUTATION FREQUENCY; TRACER TECHNIQUES; ACID ANHYDRASES; AMINES; ANIMAL CELLS; ANTI-INFECTIVE AGENTS; ANTIBIOTICS; ANTIMITOTIC DRUGS; ANTINEOPLASTIC DRUGS; AROMATICS; BIOLOGICAL EFFECTS; CONDENSED AROMATICS; DOSES; DRUGS; ENZYMES; ESTERS; HYDROCARBONS; HYDROLASES; ISOTOPE APPLICATIONS; KINETICS; MAPPING; MUTAGENS; NITROSO COMPOUNDS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANIC SULFUR COMPOUNDS; PHOSPHOHYDROLASES; RADIATION DOSES; REACTION KINETICS; SULFONIC ACID ESTERS; 560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)
Citation Formats
Adair, G M, and Carver, J H. Induction and expression of mutations at multiple drug-resistance marker loci in Chinese hamster ovary cells. United States: N. p., 1983.
Web. doi:10.1002/em.2860050206.
Adair, G M, & Carver, J H. Induction and expression of mutations at multiple drug-resistance marker loci in Chinese hamster ovary cells. United States. https://doi.org/10.1002/em.2860050206
Adair, G M, and Carver, J H. 1983.
"Induction and expression of mutations at multiple drug-resistance marker loci in Chinese hamster ovary cells". United States. https://doi.org/10.1002/em.2860050206.
@article{osti_5518870,
title = {Induction and expression of mutations at multiple drug-resistance marker loci in Chinese hamster ovary cells},
author = {Adair, G M and Carver, J H},
abstractNote = {We observed quantitative and qualitative differences in the mutability and mutagen-specificity of various drug-resistance marker loci in Chinese hamster ovary (THO) cells, which suggest that mammalian gene loci may differ in their relative mutability by a given mutagenic agent. We have used the CHO-AT3-2 multiple-marker mutagenesis assay system to examine the dose-dependent induction and kinetics of expression of mutations at four well-characterized, drug-resistance marker loci, after treatment with chemical agents which produce various types of DNA damage. The CHO-AT3-2 subline allows simultaneous quantitation and direct comparison of induced mutation frequencies at the hgprt, oua (Na/sup +//K/sup +/ ATPase), aprt, and tk loci. The agents tested in this study included ethyl methanesulfonate, methyl methanesulfonate, mitomycin C, ICR-191, benzo(a)pyrene, and dimethylnitrosamine. The expression kinetics and optimal expression times for each drug-resistance marker were determined in dose-response experiments in which cells from mutagen-treated populations were plated at 1-2-day intervals over a period of 10 days following mutagenesis. Comparison of induced mutation frequencies for each drug-resistance marker after mutagen treatments yielding equivalent cell survivals (equitoxic doses resulting in relative cell survivals of 0.37) revealed locus-specific differences in the relative mutagenicities of the agents tested. These results indicate that the apparent mutagenicity of a particular agent at a single genetic locus may not necessarily be an accurate indicator of that agent's mutagenic potential for the genome as a whole.},
doi = {10.1002/em.2860050206},
url = {https://www.osti.gov/biblio/5518870},
journal = {Environ. Mutagen.; (United States)},
number = ,
volume = 5:2,
place = {United States},
year = {Sat Jan 01 00:00:00 EST 1983},
month = {Sat Jan 01 00:00:00 EST 1983}
}