ISSN:0192-2521    

DOI:10.1002/em.2860120103

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

年代:1988

数据来源: WILEY

摘要:

AbstractBy comparing fibroblast strains derived from individuals exhibiting chromosome instability and/or mutagen hypersensitivity (Cockayne syndrome, ataxia telangiectasia, and Fanconi anemia) with strains derived from healthy donors, the fibroblast micronucleus assay has been established as a reproducible measure of the genotypic variation in spontaneous or mitomycin C (MMC)‐induced chromosomal instability. The patient strains that were moderately or exquisitely sensitive to MMC could be distinguished readily from the control strains, both in levels of spontaneous micronuclei (probably related to chromosome breakage) and in sensitivity to MMC, whereas the mildly sensitive strain (Cockayne syndrome) overlapped with the control range. The reproducibility of the assay was evaluated within and between experiments. Paired comparison analyses between duplicate cultures and between repeat experiments failed to show any significant differences between micronucleus frequencies within strains, whereas a significant difference in the spontaneous micronucleus frequencies between strains was observed. In addition to its value as a test system for genotoxins, the fibroblast micronucleus assay may be useful for investigating genetically determined hypersensitivity to mutagens, elevated spontaneous chromosomal breakage, and chromosome segregation error

ISSN:0192-2521    

DOI:10.1002/em.2860120104

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

年代:1988

数据来源: WILEY

摘要:

AbstractPrevious attempts to derive a formula for the variance of the estimated mutant fraction have assumed (without providing justification) that variance components due to treatment, growth and dilution, and plating, are additive. We have derived a variance formula that does not depend on this assumption. Our formula also includes variability attributable to imprecise counting of cells to be plated in the non‐selective condition

ISSN:0192-2521    

DOI:10.1002/em.2860120105

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

年代:1988

数据来源: WILEY

摘要:

AbstractThe C3H/10T1/2 transformation assay was evaluated for its responsiveness and interlaboratory reproducibility. Two laboratories participated in this study and tested a series of 46 chemicals. The majority of these chemicals were tested under code. Of the 46 chemicals tested, seven were determined to be active in both laboratories, and 14 were determined to be inactive. When the total number of chemicals is adjusted for assays considered “no test” in either one or both laboratories as well as for tests of chemicals yielding positive results in only one laboratory, reproducible responses were obtained for 21/35, or 60%, of the chemicals tes

ISSN:0192-2521    

DOI:10.1002/em.2860120106

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

年代:1988

数据来源: WILEY

摘要:

AbstractThree laboratories participated in an interlaboratory study to evaluate the usefulness of the Chinese hamster V79 cell metabolic cooperation assay to predict the tumor‐promoting activity of selected chemicals. Twenty‐three chemicals of different chemical structures (phorbol esters, barbiturates, phenols, artificial sweeteners, alkanes, and peroxides) were chosen for testing based on in vivo promotion activities, as reported in the literature. Assay protocols and materials were standardized, and the chemicals were coded to facilitate unbiased evaluation. A chemical was tested only once in each laboratory, with one of the three laboratories testing only 15 out of 23 chemicals. Dunnett's test was used for statistical analysis, and differences between treated‐ and control‐cell responses were analyzed atP≦.01. Chemicals were scored as positive (at least two concentration levels statistically different than control), equivocal (only one concentration statistically different), or negative. For 15 chemicals tested in all three laboratories, there was complete agreement among the laboratories for nine chemicals. For the 23 chemicals tested in only two laboratories, there was agreement on 16 chemicals. With the exception of the peroxides and alkanes, the metabolic cooperation data were in general agreement with in vivo data. However, an overall evaluation of the V79 cell system for predicting in vivo promotion activity was difficult because of the organ specificity of certain chemicals and/or the limited number of adequately tested nonpromoting

ISSN:0192-2521    

DOI:10.1002/em.2860120107

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

年代:1988

数据来源: WILEY

摘要:

AbstractEleven mutagenic heterocyclic amines, 3‐amino‐1,4‐dimethyl‐5H‐pyrido[4,3‐b]‐indole (Trp‐P‐1), 3‐amino‐1‐methyl‐5H‐pyrido[4,3]indole (Trp‐P‐2), 2‐amino‐6‐methyl‐dipyrido[1,2‐a:3′,2′‐d]imidazole (Glu‐P‐1), 2‐aminodipyrido[1,2‐a:3′,2′‐d]imidazole (Glu‐P‐2), 2‐amino‐9H‐pyrido[2,3‐b]indole (AαC), 2‐amino‐3‐methyl‐9H‐pyrido[2,3‐b]indole (MeAαC), 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ), 2‐amino‐3,4‐dimethylimidazo[4,5‐f]quinoline (MeIQ), 2‐amino‐3,8‐dimethylimidazo [4,5‐f]quinoline (MeIQX), 2‐amino‐3,4,8‐trimethylimidazo[4,5‐f]quinoxaline (4,8‐diMeIQX), and 2‐amino‐3,7,8‐trimethylimidazo[4,5‐f]quinoxaline (7,8‐diMeIQX), were studied for genotoxicity in the hepatocyte/DNA repair test employing hepatocytes of male rats, male and female mice, and male hamsters. In these four assay systems, all compounds elicited DNA repair in at least three systems, except Trp‐P‐2, which was uniformly inactive. However, there were several significant differences in the responses of different systems. Rat and hamster hepatocytes responded to nine of the ten genotoxic compounds with the exception of Glu‐P‐2. Male and female mouse hepatocytes responded to Glu‐P‐2, whereas female, but not male, mouse hepatocytes responded to MeIQX and 4,8‐diMeIQX. These results illustrate species and sex differences in re

ISSN:0192-2521    

DOI:10.1002/em.2860120108

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

年代:1988

数据来源: WILEY

摘要:

AbstractDrugs containing secondary aliphatic amines, heterocyclic nitrogen, or secondary aliphatic amido groups (chloroquine, dehydroemetine, mebendazole, and piperazine) and pyrimidine derivatives such as pyrantel pamoate were reactedin vitrowith sodium nitrite at pH 3.7 and became mutagenic forSalmonella typhimuriumstrain TA1535. The products derived from the nitrosation of chloroquine and dehydroemetine required metabolic activation by mammalian hepatic S9 to be mutagenic. TheN‐nitroso derivatives of mebendazole, piperazine, and pyrantel pamoate were mutagenic with and without S9, although more activity was noted in the presence of S9 with the nitrosated compounds formed from mebendazole and piperazine. Under identical conditions, no mutagenic products were detected from quaternary ammonium salts such as bephenium hydroxynaphthoate or drugs containing tertiary heterocyclic amino groups, such as iodochlorhydroxyqui

ISSN:0192-2521    

DOI:10.1002/em.2860120109

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

年代:1988

数据来源: WILEY

摘要:

AbstractThis report puts into perspective a series of exploratory statistical analyses carried out on the major genotoxicity data bases. While large compilations of data, even though computerized, suffer from their own size and are quite intractable to scientific reflection and judgement, the multivariate data analysis methods used by us are specifically designed for reorganising the information in a rational way and highlighting the underlying regularities of the data.The analyses reported here refer to the following data bases: the International Program for the Evaluation of Short‐Term Tests for Carcinogens, the International Program on Chemical Safety Collaborative Study on In Vitro Assays, the Gene‐Tox data base, and a subset of the U.S. National Toxicology Program data.Although the various data bases consisted of different sets of chemicals and had different underlying rationales, a number of invariant associations among short‐term test performances were highlighted. The overall evidence indicated that the traditional classification of assays (according to the criteria of genetic end‐point and phylogenetic position of the assays) was in contrast with the actual, operational similarities among assay performances, in that the experimental responses of the tests to the large variety of chemicals under consideration pointed to an alternative classification scheme. This consisted of three major classes: 1) a class comprising the in vivo assays; 2) a class grouping together many of the most widely used in vitro assays (Salmonella, chromosomal aberrations, and sister chromatid exchanges in Chinese hamster ovary cells, the various mutation tests in mammalian cell systems, etc.); 3) a second in vitro assay class (with Syrian hamster embryo cell transformation,Saccharomyces cerevisiaeXV185‐14C,B. subtilis rec‐, Escherichiacoli pol A). Such classes had clearly differentiated features with respect to carcinogenicity prediction. The implications of these findings for the current debate on mutagenicity testing ar

ISSN:0192-2521    

DOI:10.1002/em.2860120110

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

年代:1988

数据来源: WILEY

摘要:

AbstractSeventy‐two chemicals were tested for their mutagenic potential in the L5178Y tk+/−mouse lymphoma cell forward mutation assay, using procedures based upon those described by Clive and Spector (Mutat Res 44:269‐278, 1975) and Clive et al. (Mutat Res 59:61‐108, 1979). Cultures were exposed to the chemicals for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 μg/ml. The chemicals were tested at least twice. Significant responses were obtained with allyl isothiocyanate, p‐benzoquinone dioxime, benzyl acetate, 2‐biphenylamine HCl, bis(2‐chloro‐1‐methylethyl)ether, cadmium chloride, chlordane, chlorobenzene, chlorobenzilate, 2‐chloroethanol, chlorothalonil, cytarabine‐HCl, p,p′‐DDE, diazinon, 2,6‐dichloro‐p‐phenylenediamine, N,N‐diethylthiourea, diglycidylresorcinol ether, 2,4‐dimethoxy aniline‐HCl, disperse yellow 3, endosulfan, 1,2‐epoxyhexa‐decane, ethyl acrylate, ethyl benzene, ethylene thiourea, F D and C yellow Number 6, furan, heptachlor, isophorone, mercuric chloride, 4,4′‐methylenedianiline 2 HCl, methyl viologen, nickel sulfate‐6H2O, 4,4′‐oxydianiline, pentachloroethane, piperonyl butoxide, propyl gallate, quinoline, rotenone, 2,4,5,6‐tetrachloro‐4‐nitro‐anisole, 1,1,1,2‐tetrachloroethane, trichlorfon, 2,4,6‐trichlorophenol, 2,4,5‐trimetho‐xybenzaldehyde, 1,1,3‐trimethyl‐2‐thiourea, 1‐vinyl‐3‐cyclopetene dioxide, vinyl toluene, and ziram.Apart from 2‐biphenylamine‐HCl, 2‐chloroethanol, disperse yellow 3, ethylene thiourea, FD and C yellow number 6, phenol, and 1,1,2‐tetrachloroethane, rat liver S9 mix was not a requirement for these compounds.Chemicals not identified as mutagens were acid red, 11‐aminoundecanoic acid, boric acid, 5‐chloro‐o‐toluidine, coumaphos, cyclohexanone, decabromodiphenyl oxide, di(2‐ethylhexyl)adipate, ferric chloride, fluometuron, melamine, monuron, phenesterin, phthalimide, reserpine, sodium dodecyl sulfate, 4,4‐sulfonyldianiline, tetrachloroethylene, and zearalenone.The assay was incapable of providing a clear indication of whether some chemicals were mutagens; these

ISSN:0192-2521    

DOI:10.1002/em.2860120111

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.2860120102

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

年代:1988

数据来源: WILEY