Use of liver cell cultures in mutagenesis studies
A sensitive cell-mediated assay has been developed for testing the mutagenesis of liver carcinogens. Mutagenesis was detected in Chinese hamster V79 cells that were cocultivated with hepatocytes isolated after collagenase/hyaluronidase digestion of rat liver slices. Mutations were characterized by resistance to ouabain and 6-thioguanine. Seven of the nitrosamines, which are potent liver carcinogens, exhibited a mutagenic response. Mutagenesis with these carcinogens could be detected at ..mu..molar doses. The polyaromatic hydrocarbon benzo(a)pyrene, which is not a liver carcinogen, but can cause fibrosarcomas, was not mutagenic in this assay, but was mutagenic in a fibroblast-mediated assay. The liver carcinogen, aflatoxin B/sub 1/, which usually does not induce fibrosarcomas, exhibited an inverse situation; it was mutagenic for V79 cells in the presence of liver cells but not in the presence of fibroblasts. We suggest that the use of various cell types, including hepatocytes prepared by the slicing method for carcinogen metabolism, and mutable V79 cells offers a sensitive assay for determining the mutagenic potential of chemical carcinogens, and may also allow a study of their organ specificity.
- Research Organization:
- Oak Ridge National Lab., TN
- DOE Contract Number:
- W-7405-ENG-26
- OSTI ID:
- 5792009
- Journal Information:
- Ann. N.Y. Acad. Sci.; (United States), Vol. 349
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
AFLATOXIN
TOXICITY
BENZOPYRENE
CELL CULTURES
MUTAGENESIS
NITROSAMINES
CARCINOGENESIS
DOSE-RESPONSE RELATIONSHIPS
FIBROBLASTS
HAMSTERS
LIVER
MUTAGEN SCREENING
MUTATIONS
SENSITIVITY
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
BODY
CONDENSED AROMATICS
CONNECTIVE TISSUE CELLS
DIGESTIVE SYSTEM
GLANDS
HYDROCARBONS
MAMMALS
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
RODENTS
SCREENING
SOMATIC CELLS
VERTEBRATES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)
550300 - Cytology
550400 - Genetics