Quantitative mammalian cell mutagenesis and mutagen screening: study with CHO cells

Conference · Mon Jan 01 00:00:00 EST 1979

OSTI ID:5830385

Hsie, A. W.; O'Neill, J. P.; San Sebastian, J. R.; Brimer, P. A.

The CHO/HGPRT system has been developed and defined for quantifying mutation induced by various physical and chemical agents at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in Chinese hamster ovary (CHO) cells. In all direct-acting chemical mutagens studied, mutation induction increases linearly as a function of the concentration, with no apparent threshold. Some chemicals induce mutation at non-cytotoxic concentrations. The mutagenicity of ethyl methanesulfonate has been quantified as a function of exposure concentration x treatment time. The sensitive and quantitative nature of the system enables studies of the structure-activity (mutagenicity) relationships of various classes of chemicals, including alkylating agents, heterocyclic nitrogen mustards, and platinum compounds. When rat liver S/sub 9/-mediated metabolic activation is present, procarcinogens such as benzo(a)pyrene, 2-acetylaminofluorene, and dimethylnitrosamine are mutagenic, whereas their noncarcinogenic structural analogues pyrene, fluorene, and dimethylamine are not. The system has been shown to be useful in determining the interactive effects between physical and chemical agents, and in screening for mutagenicity of fractionated organic mixtures and industrial chemicals in both liquid and gaseous state. For the system to be used successfully in routine screening, further studies should be directed toward the development of a metabolic activation system suitable for a broad spectrum of chemicals, a sensitive and reliable statistical method, and an experimental design to determine compounds with low mutagenicity. The system has been expanded for determination of mutagen-induced chromosome aberration, sister-chromatid exchange, and micronucleus formation in addition to gene mutation and cytotoxicity; it can also be used to study inhibition of DNA synthesis. (ERB)

• Research Organization: Oak Ridge National Lab., TN (USA); Tennessee Univ., Oak Ridge (USA). School of Biomedical Sciences
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 5830385
• Report Number(s): CONF-790951-1; TRN: 80-002201
• Resource Relation: Conference: NATO advanced research institute on in vitro toxicity for environmental agents, Monte Carlo, Monaco, 22 Sep 1979
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
ADDITIVES
MUTAGENESIS
ANIMAL CELLS
MUTATIONS
IONIZING RADIATIONS
MUTAGEN SCREENING
DOSE-RESPONSE RELATIONSHIPS
ALKYLATING AGENTS
CELL CULTURES
CELL KILLING
CHEMICAL EFFLUENTS
CHROMOSOMAL ABERRATIONS
HAMSTERS
MUTAGENS
NITROGEN MUSTARD
PLATINUM COMPOUNDS
SISTER CHROMATID EXCHANGES
TOXICITY
AMINES
ANIMALS
ANTIMITOTIC DRUGS
DRUGS
MAMMALS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
RADIATIONS
RODENTS
SCREENING
TRANSITION ELEMENT COMPOUNDS
VERTEBRATES
560121* - Radiation Effects on Cells- External Source- (-1987)
560302 - Chemicals Metabolism & Toxicology- Microorganisms- (-1987)
550400 - Genetics