ISSN:0192-2521    

DOI:10.1002/em.2860060602

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

年代:1984

数据来源: WILEY

ISSN:0192-2521    

DOI:10.1002/em.2860060603

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

年代:1984

数据来源: WILEY

ISSN:0192-2521    

DOI:10.1002/em.2860060604

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

年代:1984

数据来源: WILEY

摘要:

AbstractChemicals capable of inducing heritable chromosomal effects may be detected by the mouse heritable translocation test, which is based on the detection of a specific type of transmissible abnormality, namely, reciprocal translocation. Since mice carrying such a chromosomal abnormality usually have reduced fertility, they may be identified on the basis of fertility data. In the present study, the efficiency of two female strains for identifying CD‐1 male translocation heterozygotes was examined. Thirty‐three 10‐wk‐old CD‐1 male mice were injected IP with triethylenemelamine (0.025 mg/kg/day) 5 days a wk for 5 wk. The treated males were then mated to untreated CD‐1 females for 2 wk to produce progeny. The F1males were raised to maturity, tested for fertility by using two female strains (CD‐I and B6C3F1), and analyzed cytogenetically. The cytogenetic analysis confirmed that 41 males were translocation heterozygotes and 125 were normal. Examination of the fertility data showed that in the test with CD‐I females all translocation heterozygotes were identified but 19 normal mice were identified as potential translocation carriers because of decreased fertility. In the test with B6C3F1 females, five translocation heterozygotes were not identified on the basis of fertility data, and 11 normal mice were misclassified as potential translo

ISSN:0192-2521    

DOI:10.1002/em.2860060605

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

年代:1984

数据来源: WILEY

摘要:

AbstractA standard protocol for theyellow‐green‐2 (yg2) forward mutation assay inZea maysis proposed. A detailed calibration of the assay using137Cs gamma rays and ethylmethanesulfonate (EMS) was conducted. Gamma ray‐induced mutant sectors in leaves 4 and 5 exhibited one‐hit kinetics. The radiation doses ranged from 25 to 500 rads. The mean induced mutation rate per rad of gamma radiation was 4.54 × 10−6. This value was constant for the primordial cells of leaves 4 or 5. The induction of forward mutation by EMS also exhibited one‐hit kinetics in the concentration range 0.25–20 mM (0.33–23.54 μmol EMS/kernel). The mean induced mutation rate per mM EMS was 1.79 × 10−4, and the mean induced mutation rate per μmol of EMS per kernel was 1.52 × 10−4. Using the induced mutation rates for gamma radiation and EMS, the rad equivalent was calculated. One rad of gamma radiation is equivalent to the exposure of a 2.53 × 10−5M EMS solution or to 2.99

ISSN:0192-2521    

DOI:10.1002/em.2860060606

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

年代:1984

数据来源: WILEY

摘要:

AbstractSeventeen structurally homologous nitroaromatics were tested for direct‐acting mutagenic potency in nine strains ofSalmonella typhimurium.The following four structural features were determined to have a strong influence on mutagenic activity: physical dimensions of the aromatic rings, isomeric position of the nitro group, conformation of the nitro group with respect to the plane of the aromatic rings, and ability to resonance‐stabilize the ultimate electrophile. Progressive addition of five‐ and six‐membered rings to a nitrobenzene nucleus demonstrated that mutagenic activity was a direct function of size. Fluoranthene was of optimal size (four rings) for mutagenicity; an additional benzene ring, giving benzo[k]fluoranthene, reduced mutagenic activity. Nitroaromatics with a nitro group oriented along the long axis of symmetry of the molecule were more potent mutagens than those with the nitro group oriented along the short axis. These results are discussed in light of the insertion‐denaturation model for intercalation of certain DNA adducts. Nitroaromatics with nitro groups sterically forced out of the plane of the aromatic rings were weakly mutagenic or nonmutagenic. Nitro groups located between two peri hydrogens or in a bay‐region are examples of this conformation. Finally, structural features that contribute to resonance stabilization of the reactive nitrenium ion enhance mutagenic potency. Thus, 6‐nitroindene was at least tenfold more mutagenic than 5‐nitroindene. These positional isomers are structurally identical with the exception of the position of an olefinic bond in the adjacent five‐membered ring which can contribute to resonance stabilization of a carbonium ion formed after bioactivation of 6‐nitroindene but not of 5‐nitroindene. The predictive value of these structure‐activity relationships should permit a first approximation in the assessment of mutagenic po

ISSN:0192-2521    

DOI:10.1002/em.2860060607

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

年代:1984

数据来源: WILEY

摘要:

AbstractMutagenic activities of a sample of characterized airborne particulates collected in a rural location near Ispra (Italy) during the summer of 1980 were detected by the Ames test using TA 1537, TA 1538, TA 98, and TA 100Salmonellastrains. Eight chemical classes fractionated from the CH2Cl2extract of the particulates were bioassayed, and their mutagenicities (TA 98 plus S9) were as follows: organic bases I>polar neutrals>insolubles in cyclohexane>organic acid II>aerosol “in toto”>intermediate neutrals>polycyclic aromatic hydrocarbons>organic acids I>nonpolar neutrals.Periodical samples were taken in the same location from March to December 1981, extracted in dimethyl sulfoxide (DMSO), and directly tested with TA 1537, TA 98, and TA 100Salmonellastrains. For all the strains the mutagenicity varied markedly according to the season, the cold‐month samples being much more mutagenic than the summer‐month samples. The additional of S9 increased the mutagenicity (twofold) of the cold‐month samples. The higher mutagenicity of the samples collected during the cold months could be due to greater amounts of mutagens produced by the combustion processes of domesti

ISSN:0192-2521    

DOI:10.1002/em.2860060608

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

年代:1984

数据来源: WILEY

摘要:

AbstractExtracts of three complex organic environmental mixtures, two from an experimental coal gasifier (a raw gas and a clean gas sample) and one from a coke oven main, were examined for genotoxicity. Three short‐term genotoxicity assay systems were used: AmesSalmonella typhimuriumreverse mutation assay, Chinese hamster ovary cell/hypoxanthine‐guanine phosphoribosyl transferase (CHO/ HGPRT) gene locus mutation assay, and the Chinese hamster lung primary culture/sister chromatid exchange (CHL/SCE) assay. Aroclor‐1254‐induced rat liver homogenate fraction (S‐9) was required to observe genotoxicity in both gene locus mutation assays (CHO/HGPRT and Ames). The relative survival of CHO cells exposed to extracts was highest in cells exposed to clean gas samples, with the raw gas sample being the most cytotoxic either with or without the addition of S‐9. All three complex mixtures induced sister chromatid exchanges in primary lung cell cultures without the addition of S‐9. The relative genotoxicity ranking of the samples varied between the mammalian and prokaryotic assay systems. Coke oven main extract produced fewer revertants in bacteria than the raw gas sample. However, the coke oven main extract was more genotoxic in the two eukaryotic systems (CHL/SCE and CHO/HGPRT) than was the raw gas sample. The results of all three assays indicate that the cleanup process used in the experimental gasifier was effective in decreasing the genotoxic materials in the process stream. These data also reemphasize the necessity of evaluating genotoxicity of complex mixtures in a variety of short

ISSN:0192-2521    

DOI:10.1002/em.2860060609

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

年代:1984

数据来源: WILEY

摘要:

AbstractNitrosamides and nitrosocarbamates exhibit relatively high mutagenic activity inSalmonellawhen compared with nitrosoureas. This high activity can be accounted for by activation of nitrosamides and nitrosocarbamates by cellular thiols, predominantly reduced glutathione, that are present intracellularly at concentrations in the millimolar range. In striking contrast to the in vitro mutagenicity tests, a number of studies have indicated that nitrosamides and nitrosocarbamates are less potent than nitrosoureas when tested in vivo in model systems such as the mouse. We extend here previous studies [Aukerman et al, 1983] that demonstrate striking chemical decomposition and inactivation of mutagenic activity of nitrosamides and nitrosocarbamates during exposure to murine blood plasma. Plasma glutathione concentrations are inadequate to account for the rapid inactivations noted. Furthermore, the predominant inactivating species is heat‐sensitive, nondialyzable, and is greater than 25,000 daltons in size as judged by ultrafiltration experiments. Serum albumin has some inactivating capacity at the concentration found in undiluted plasma and could account for the very low but significant inactivating capacity of human plasma. On the other hand, serum albumin lacks the potency necessary to account for the extremely high levels of inactivating activity observed in rodent and rabbit plasma. Elsewhere we present evidence that carboxylesterase activity is the predominant inactivating species in mouse plasma [Aukerman et al, 1983; Aukerman, 1983; Brundrett and Aukerman, 1984]. Mouse liver, large intestine, kidney, and stomach have more activity per milligram protein under the assay conditions used than plasma itself. Rat liver S9 is also active at enhancing the decomposition of nitrosamides and nitrosocarbamates; most of this inactivating capacity resides in the microsomal fraction. The relatively rapid detoxification of these N‐nitroso compounds by plasma and other tissues of rodents has important implications regarding the utility of rodents in assessment of tumorigenicity and/ or antitumor activity of these classes of drugs in other animal species. Tests withSalmonellamay be of use in estimating relative levels of protection that vary widely among mammalian spec

ISSN:0192-2521    

DOI:10.1002/em.2860060610

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

年代:1984

数据来源: WILEY

摘要:

AbstractKat is being used extensively in many countries as a central nervous system stimulant. The effect of three doses of crude kat extract on chromosomal division and abnormalities in bone marrow, as well as on DNA, RNA, and total protein content in brain and liver was studied in laboratory rats in order to test the possible mutagenicity of the drug. Kat was given as a single subcutaneous injection at 0.05 (usage dose), 0.52 (intermediate dose), and 1.00 (sublethal dose) g/kg body weight. Animals were sacrificed at 6, 24, and 48 hr after treatment. Also, some animals were exposed subacutely for 5 consecutive days with sacrifice occurring 6 hr after the last injection. The mitotic index was reduced by all treatments, with the greatest effect occurring in the subacute treatment. Chromosomal abnormalities were induced by kat at all three doses, administered acutely or subacutely. The significant chromosomal aberrations were in the form of gaps, breaks, centromeric attenuations, and centric fusions. The concentration of DNA, RNA, and total protein in liver and brain decreased at all doses, with the greatest decrease occurring after subacute treatment. These findings suggest that kat has a profound effect on cell proliferation, on chromosomal abnormalities, and on DNA, RNA, and total protein synthesis.

ISSN:0192-2521    

DOI:10.1002/em.2860060611

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

年代:1984

数据来源: WILEY