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), Journal Name: Ann. N.Y. Acad. Sci.; (United States) Vol. 349; ISSN ANYAA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Liver cell-mediated mutagenesis of mammalian cells by liver carcinogens. [Carcinogen screening method]
Induction of mutagenesis and alterations in gene expression by tumorigenic chemicals
Related Subjects
550400 -- Genetics
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AFLATOXIN
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
BENZOPYRENE
BODY
CARCINOGENESIS
CELL CULTURES
CONDENSED AROMATICS
CONNECTIVE TISSUE CELLS
DIGESTIVE SYSTEM
DOSE-RESPONSE RELATIONSHIPS
FIBROBLASTS
GLANDS
HAMSTERS
HYDROCARBONS
LIVER
MAMMALS
MUTAGEN SCREENING
MUTAGENESIS
MUTATIONS
NITROSAMINES
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
RODENTS
SCREENING
SENSITIVITY
SOMATIC CELLS
TOXICITY
VERTEBRATES