Quantitative mammalian cell mutagenesis and a preliminary study of the mutagenic potential of metallic compounds. [Cell system used was CHO/HGPRT]

Conference · Sun Jan 01 04:00:00 EST 1978

OSTI ID:6201762

Hsie, A. W.; Johnson, N. P.; Couch, D. B.; San Sebastian, J. R.; O'Neill, J. P.; Forbes, N. L.

We have defined a set of stringent conditions required to quantify specific gene mutation in a mammalian cell system, CHO/HGPRT. Greater than 98% of the 6-thioguanine (TG)-resistant variants were shown to be deficient in the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity in Chinese hamster ovary (CHO) cells. The sensitive and quantitative nature of this assay was utilized to study the structure-activity (mutagenicity) relationship of various classes of chemicals. Mutagenicity as determined in the CHO/HGPRT assay, appears to correlate well (76/83 (92%)) with the reported animal carcinogenicity of 108 chemicals studied. The system also appears to be suitable for studying the mutagenicity and cytotoxicity of metallic compounds. We found that cis-dichlorodiammine Pt(II) (cis-Pt(NH/sub 3/)/sub 2/Cl/sub 2/) (cis-DDP), one of the widely used inorganic antitumor agents, is cytotoxic and mutagenic. Mutagenicity of cis-DDP correlates with its binding to DNA. However, trans-DDP, (Pt(NH/sub 3/)/sub 4/)Cl/sub 2/, and K/sub 2/(PtCl/sub 4/) exhibit greatly reduced biological activities. Among 14 other metals studied, we found that carcinogenic metallic compounds, such as MnCl/sub 2/, NiCl/sub 2/, and BeSO/sub 4/ are mutagenic, while non-carcinogenic compounds such as MgCl/sub 2/ and H/sub 2/SeO/sub 3/ are not. Determination of metal mutagenicity is apparently complicated by the ionic composition of the medium. This may account in part for varying results in studies of the mutagenicity of other metallic compounds. Further refinement of the assay conditions, especially with respect to the ionic environment necessary for quantifying mutagenesis of each metallic agent, is in progress.

• 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: 6201762
• Report Number(s): CONF-7811110-1
• Country of Publication: United States
• Language: English

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.
ALKALI METAL COMPOUNDS
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
BERYLLIUM COMPOUNDS
BERYLLIUM SULFATES
CADMIUM CHLORIDES
CADMIUM COMPOUNDS
CADMIUM HALIDES
CELL CULTURES
CHALCOGENIDES
CHLORIDES
CHLORINE COMPOUNDS
COPPER COMPOUNDS
COPPER SULFATES
GENE MUTATIONS
HALIDES
HALOGEN COMPOUNDS
IRON COMPOUNDS
IRON SULFATES
LEAD COMPOUNDS
MAGNESIUM CHLORIDES
MAGNESIUM COMPOUNDS
MANGANESE CHLORIDES
MANGANESE COMPOUNDS
MANGANESE HALIDES
MEASURING METHODS
MUTAGEN SCREENING
MUTAGENESIS
MUTATIONS
NICKEL CHLORIDES
NICKEL COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
PLATINUM COMPOUNDS
RUBIDIUM CHLORIDES
RUBIDIUM COMPOUNDS
SCREENING
SELENIUM COMPOUNDS
SELENIUM OXIDES
SILVER COMPOUNDS
SILVER SULFATES
SULFATES
SULFUR COMPOUNDS
TITANIUM CHLORIDES
TITANIUM COMPOUNDS
TRANSITION ELEMENT COMPOUNDS
ZINC COMPOUNDS
ZINC SULFATES