Comparison of mutagenicity results for nine compounds evaluated at the hgprt locus in the standard and suspension CHO assays.
The Chinese hamster ovary (CHO) assay, which measures newly induced mutations at the hypoxanthine-guanine phosphoribosyltransferase (hgprt) locus, has been widely used for mutagenesis testing. The insensitivity of the standard assay to some genotoxic agents has been speculated to be due to the relatively small number of cells used in the assay. In the present study, we have compared the standard monolayer assay with a suspension adapted CHO assay that uses cell numbers comparable to that of the L5178Y mouse lymphoma assay. Nine compounds, ethyl methanesulfonate (EMS), methyl methanesulfonate (MMS), 2-methoxy-6-chloro-9-[3-(ethyl-2-chloroethyl)-aminopropylamino]-acridine 2HCl (ICR 170), methyl acrylate, ethyl acrylate, tetraethylene glycol diacrylate, trimethylolpropane triacrylate, 2-ethylhexyl acrylate and dicyclopentenyloxyethyl methacrylate were evaluated in the monolayer and suspension assays. Both assays gave the same overall qualitative results for the test compounds. There were some quantitative differences in the mutant frequency for the three compounds found to be mutagenic (EMS, MMS and ICR 170). The acrylates (many of which appear to exert their genotoxic effect through a clastogenic mechanism) were negative in both test systems. The use of the suspension assay did not improve the ability of the hgprt locus to detect the genotoxicity of the acrylates. Thus, increasing the number of cells does not improve the ability of the CHO/HGPRT assay to detect compounds that act primarily by a clastogenic mechanism.
Moore
M M
MM
Mutagenesis and Cellular Toxicology Branch, Environmental Protection Agency, Research Triangle Park, NC 27711.
Parker
L
L
Huston
J
J
Harrington-Brock
K
K
Dearfield
K L
KL
D000179:Acrylates / Q000633:toxicity; D000609:Aminoacridines; D000818:Animals; D002460:Cell Line; D002869:Chromosome Aberrations; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005020:Ethyl Methanesulfonate / Q000633:toxicity; D005260:Female; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008223:Lymphoma; D008741:Methyl Methanesulfonate / Q000633:toxicity; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D009588:Nitrogen Mustard Compounds / Q000633:toxicity
D000179:Acrylates; D000609:Aminoacridines; D009153:Mutagens; D009588:Nitrogen Mustard Compounds; C091910:acridine mustard; D005020:Ethyl Methanesulfonate; D008741:Methyl Methanesulfonate; D007041:Hypoxanthine Phosphoribosyltransferase