Induction and expression of mutations at multiple drug-resistance marker loci in Chinese hamster ovary cells
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.
- Research Organization:
- Univ. of Texas System Cancer Center, Smithville
- DOE Contract Number:
- W-7405-ENG-48
- OSTI ID:
- 5518870
- Journal Information:
- Environ. Mutagen.; (United States), Vol. 5:2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
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)