Human Epithelial Cell Metabolic Activation Systems for Use with Human Cell Mutagenesis.
NIOSH 1980 May:306-326
Human epithelial cell metabolic activation systems were developed for use in the diploid human fibroblast cell mutagenesis system. Human tumor cell lines were prescreened for their ability to metabolize a variety of test chemicals by determining interference with DNA synthesis. Compounds under study were administered to the metabolizing cells over a wide range of concentrations and incubated for 48 hours. The amount of semiconservative DNA synthesis was measured by incorporation of labeled thymidine and compared with synthesis of untreated control cells. Cell lines activating a particular chemical were examined for their ability to act as a metabolizing layer for target cells. Target cells in the cocultivation system primarily were excision repair defective XP cells which were examined for evidence of cell killing. Normal fibroblasts were used effectively as target cells once conditions were optimized. The prescreen was used to identify cells capable of activating a wide range of agents including polycyclic aromatic hydrocarbons, aflatoxins, aromatic amides and amines, nitrosamines, and nitrogen containing polycyclics. The authors conclude that DNA adducts can be produced by the activation system similar to those produced in-vivo.
Mammalian-cells; Biochemical-tests; Screening-methods; In-vivo-studies; Humans; Mutagenesis;
Proceedings of the First NCI/EPA/NIOSH Collaborative Workshop: Progress on Joint Environmental and Occupational Cancer Studies, May 6-8, 1980, Rockville, Maryland, H. F. Kraybill, I. C. Blackwood, and N. B. Freas, Eds., National Cancer Institute, Environmental Protection Agency, National Institute for Occupational Safety and Health