Mutagenesis testing with mammalian cells: validating and adapting a multiple-marker bioassay to activate and detect mutagens in crude samples for energy technology. Progress report, January-June 1979
A Chinese hamster ovary (CHO) cell line heterozygous at both the adenine phosphoribosyltransferase (aprt) and thymidine kinase (tk) loci was used for single-step selection of spontaneous and induced mutants resistant to 8-azaadenine, 6-thioguanine, ouabain, or 5-fluorodeoxyuridine. Mutation data are reported for direct mutagens and promutagens activated by rat liver homogenates. The induced mutant frequencies as a function of relative cell survival after treatment with EMS, DMN, or BP showed locus-specific differences in sensitivity. A very high percentage of the spontaneous and induced drug-resistant clones scored as mutants had substantially diminished enzyme activity at the selected locus. The tk locus showed the largest mutational response. The rapid expression kinetics for FUdR/sup r/ and the possibility that the locus detects a broader spectrum of genetic lesions than the other drug-resistance markers are discussed in terms of a sensitive screening assay for detecting potential mutagens. Four carcinogens were identified as mutagens, and two non-carcinogens were not mutagenic in the system. Two reported non-carcinogens were identified as mutagenic in the system. Four carcinogens that are reported to give negative or erratic results in Salmonella and/or cell transformation assays were negative also in this system. Ethylenethiourea failed to give the expected positive result when tested in this system. To solve the solubility problems encountered with compounds in the International Program, protocols were developed to allow higher concentrations of mutagen exposure by means of dispersal in corn oil emulsions. The techniques are currently being applied to studies on trichlorethylene. (ERB)
- Research Organization:
- California Univ., Livermore (USA). Lawrence Livermore Lab.
- DOE Contract Number:
- W-7405-ENG-48
- OSTI ID:
- 6007452
- Report Number(s):
- UCID-18080-79-1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
MUTATIONS
CARCINOGENS
MUTAGEN SCREENING
MUTAGENS
CELL CULTURES
EXPERIMENTAL DATA
HAMSTERS
ISOLATED VALUES
MUTAGENESIS
ANIMALS
DATA
DATA FORMS
INFORMATION
MAMMALS
NUMERICAL DATA
RODENTS
SCREENING
VERTEBRATES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)
550400 - Genetics