摘要:

AbstractA general protocol, modified from the one described by Clive and Spector (Mutat Res 31:17–29, 1975), was followed by two laboratories, Litton Bionetics, Inc., and SRI International, to evaluate 63 coded chemicals from 16 chemical classes for mutagenic activity at the thymidine kinase locus in L5178Y TK±3.7.2C mouse lymphoma cells. The general protocol is discussed. Some procedural variations introduced by both laboratories are described and discussed in terms of their potential effect on the comparative results of the assay. Also included are the chemical structures, molecular weights, and functional classifications of the 63 chemicals. The assay appeared to tolerate the specific procedural variations in each laboratory without changing its reliabili

ISSN:0192-2521    

DOI:10.1002/em.2860120502

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractA data‐based approach to formulating quality‐control criteria for the mouse lymphoma cell forward mutation assay is described. Quality‐control guidelines for solvent controls, positive controls, and compound‐treated cultures were developed based on analysis of over 800 experiments. Frequency distributions of experimental parameters of control cultures, such as mutant frequencies, cloning efficiencies, and suspension growths, were examined. Cloning efficiency and relative total growth affected the variability only when the test chemical was highly toxic. This information was used to generate the quality‐control criteria, which were applied to an experiment before it was evaluated for a response. The response categories for classifying the effect of test chemicals on the assay system are defined in terms of (1) the statistically significant differences in average mutant frequency between solvent control cultures and cultures exposed to a chemical and (2) the trend of the dose‐relate

ISSN:0192-2521    

DOI:10.1002/em.2860120503

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractSRI used the L5178Y mouse lymphoma cell forward mutation assay to determine the mutagenic activity of 63 coded chemicals from 16 chemical classes. Replicate experiments were performed to assess the reproducibility of the assay within the laboratory. The evaluations (positive or negative) of the first two repeat experiments with the chemicals were the same for 116 (87%) of 134 tests. Evaluational differences between the first two experiments were fewer in the presence of induced S9 (6 tests) than in the absence of S9 (12 tests). The most commonly observed variability was the magnitude of positive mutagenic responses; this may be attributed to factors such as compound solubilities, S9 activation conditions, and differential recovery of mutant cells. Some consistency was observed in the responses of compounds of various chemical classes. Generally, antibiotics (ABO) and the azo dyes, azoxy and hydrazo compounds, diazoalkanes, nitriles and azides (AZO), were mutagenic with S9; alkyl, acyl, and aryl halides, halogenated ethers, and halohydrins (HAL) were more strongly mutagenic with than without S9; and monofunctional polycyclic aromatic hydrocarbons and fluorenones (PAH) were mutagenic only with S9. Amine‐1‐oxides (AMO), alkyl and aryl epoxides (EPO), and nitroalkanes, nitroaromatics, nitroquinolines, nitrofurans, and nitroimidazoles (NIT) were mutagenic with and without S9; amides, sulfonamides, aromatic amines, aliphatic amines, hydroxylamines, and benzidine and its derivatives (AMI) were mutagenic without S9; and methyl carbamate (the only monofunctional carbamate) and thioureas (CBM) induced a negative response under both conditi

ISSN:0192-2521    

DOI:10.1002/em.2860120504

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThe reliability of the L5178Y TK±forward mutation assay as a rapid screen for genotoxicity was evaluated by testing 63 coded chemicals. Replicate treatments were used, and at least two independent experiments were performed for each test condition. The test conditions consisted of no exogenous activation, activation by Aroclor 1254‐induced Fischer 344 rat liver S9 homogenate, and in some cases activation by noninduced Fischer 344 rat liver S9. The results were organized into tables that show the mutant colony counts, mutant frequency, and toxicity for each test chemical treatment, positive control treatment, and solvent negative control cultures. The repeat experiments were highly consistent and yielded contradictory evaluations for only a few of the chemicals studied. Fifty‐one of the chemicals (81%) were evaluated as mutagenic under one or both of the test conditions. A range in minimum effective concentrations of almost 106‐fold (0.008 to 5,000 μg/ml) was observed among the mutagenic chemicals. Nine chemicals (14%) were considered to be nonmutagenic. Three chemicals (progesterone,p‐rosaniline HCl, and 1,1,1‐trichloroethane) gave responses that were not easily evaluated under any test condition: evidence for mutagenesis was obtained in some experiments but not for all repeat studies. Under nonactivation conditions, specifically, the mutagenic activities of 4,4′‐bis(dimethylamino)benzophenone, progesterone, andp‐rosaniline HCl remained uncertain. With S9 activation, uncertain evidence for mutagenesis was obtained for 2‐naphthylamine, progesterone, and 1,1,1‐trichloroethane. In some cases, changes in the treatment conditions could lead to different evaluations of the mutagenic activity, and these possibilities are discussed in the descriptive evaluations of each chemical. Comparisons of the observed responses with published results were possible for 29 of the compounds and yielded highly con

ISSN:0192-2521    

DOI:10.1002/em.2860120505

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

摘要:

AbstractThe L5178Y mouse lymphoma cell mutagenesis assay is used to detect the mutagenic activity of chemicals in a mammalian cell system. To evaluate this assay we compared the results of assays performed independently on 63 chemicals by laboratories at SRI International and Litton Bionetics, Inc. The two laboratories used similar protocols. The solvent and positive control mutant frequencies and cloning efficiencies obtained by the two laboratories were similar, which justified the use of the same quality‐control criteria and analytical procedures for analyzing the results from both laboratories. The rate of concordance between the two laboratories was 92% for tests in the absence of S9 activation and 95% for tests in its presence. The results of the assays agreed for 57 of the 63 chemicals; three chemicals could not be compared because there were questionable calls in at least one of the laboratories; the results disagreed for the three remaining chemicals. The concordance rate for these overall assay evaluations was 95%. The interlaboratory concordance rates were similar to concordance rates for replicate experiments within the laboratories (96% at LBI, 94% at SRI). The mouse lymphoma cell mutagenicity results are concordant with the rodent chronic assay results in 78% of 50 chemicals and with theSalmonellaassay results in 79% of 56 chemicals. Fifteen carcinogens were examined for genotoxic effects in mouse lymphoma,Salmonella, Chinese hamster ovary (CHO) chromosomal aberration, and CHO sister chromatid exchange assay. Eight of these were positive in all four assays. Of the seven noncarcinogens that were tested in these four assays, none was negative in all four. The main conclusion to be drawn from this study is that the mouse lymphoma cell forward mutation assay, as performed and evaluated i

ISSN:0192-2521    

DOI:10.1002/em.2860120506

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY

ISSN:0192-2521    

DOI:10.1002/em.2860120501

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1988

数据来源: WILEY