摘要:

AbstractTo estimate the absorbed dose of N‐ethyl‐N‐nitrosourea (ENU) ingested inDrosophila melanogaster, males were fed with sucrose solutions containing various concentrations of ENU plus3H‐labeled sucrose for 24 hr. Flies showed decreasing intakes with increase in ENU concentration when monitored by intake3H radioactivity. Absorbed dose,D, per male can be estimated by the following formula:D=vμC, wherevis intake volume per male of sucrose solution at concentration C. Estimating the v value for each ENU solution from3H radioactivities in male flies, and using the above formula, we reached the conclusion that average absorbed doses of ENU were 0.064, 0.221, and 0.302 nmol, respectively, for the ENU concentrations of 0.03, 0.3, and 1.0 mM. Sex‐linked recessive lethals were measured for males exposed to these sucrose solutions at three different ENU concentrations. Their frequencies increased nonlinearly with increasing exposure doses—ie, ENU concentrationC—but linearly with increasing absorbed doses estimated in the above

ISSN:0192-2521    

DOI:10.1002/em.2860060402

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

年代:1984

数据来源: WILEY

摘要:

AbstractInduction of recessive lethal mutations by N‐ethyl‐N‐nitrosourea (ENU) was studied for the second chromosome of spermatogonia and spermatozoa inDrosophila melanogaster.ENU (0.03,0.3, and 1.0 mM) was given to flies by dissolving it in feeding sucrose solution. Since flies are known to show increased avoidance of the feeding solution with increase in ENU concentration, the absorbed doses of ENU by flies were estimated from the previously determined empirical data for relation of ENU concentration in the feeding solution and the intake volumes of the solution by flies as measured indirectly via intake radioactivities of3H‐labeled sucrose added to the solution. When plotted against absorbed doses of ENU, the observed frequencies of recessive lethals showed a linear relationship for induction in spermatozoa but a sigmoidal relationship for induction in spermatogonia. These results suggest that in spermatogonia ENU‐induced mutational damage is more repairable in a lower dose range of ENU. Mosaic lethal mutations were induced by ENU but not in sper

ISSN:0192-2521    

DOI:10.1002/em.2860060403

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

年代:1984

数据来源: WILEY

摘要:

AbstractThe isomers of various two‐, three‐, and four‐ring amino polycyclic aromatic hydrocarbons were tested for mutagenic activity using a microbial plate incorporation test with fourSalmonella typhimuriumstrains (TA98, TA 100, TA1535, and TA 1537). All compounds were assayed with an S9 metabolic activating enzyme system. The two‐ring compounds were tested only with TA98. All were weakly mutagenic (1–10 rev/μg) except 2‐aminobiphenyl, which was not mutagenic under these test conditions. All except two of the 13 fused three‐ring compounds (aminofluorenes, aminoanthracenes, and aminophenanthrenes) were active frame shift mutagens; only the aminophenanthrenes were active base‐pair mutagens. The potency of this group of isomeric compounds ranged from moderately (˜ 20 rev/μg) to strongly (>5,000 rev/μg) mutagenic. As a group, the pericondensed fourring amino compounds were the most mutagenic of the three groups tested. All of the aminofluoranthene and aminopyrene isomers showed significant mutagenic activity with TA98, TA100, and TA1537. In general, the mutagenic potency of the amino polycyclic aromatic compounds tested was highly dependent on the structural position

ISSN:0192-2521    

DOI:10.1002/em.2860060404

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

年代:1984

数据来源: WILEY

摘要:

AbstractWe used the Chinese hamster ovary cell/hypoxanthine‐guanine phosphoribosyl‐transferase (CHO/HGPRT) assay to determine the cytotoxicity and mutagenicity of a crude coal oil, the neutral fraction of this crude, and the following three subtractions of the neutral fraction: aliphatic, neutral polar, and a subtraction composed of polycyclic aromatic hydrocarbons plus neutral nitrogen heterocyclics. We also studied the cytotoxicity and mutagenicity of a blend of light and heavy coal‐derived fuel oils before and after hydrogenation. All seven mixtures were highly cytotoxic to CHO cells, but the addition of S9 reduced the cytotoxicity. Also, hydrogenation reduced the cytotoxicity of the blend of coal‐derived fuel oils. Although highly cytotoxic, none of the seven mixtures induced a clear mutagenic response in the CHO/HGPRT assay. However, previous work has shown that all of the mixtures except the aliphatic subfraction and the blend after hydrogenation are mutagenic in the histidine‐reversion assay inSalmonella typhimurium.Based on chemical analyses of the mixtures, the differential sensitivity ofSalmonellaand CHO cells to nonmutagenic cytotoxins, and studies of the neutral fraction to which additional benzo[a]pyrene had been added, we conclude that the disparity between the results inSalmonellaand those obtained in the CHO/HGPRT assay is probably due to the much greater sensitivity of CHO cells (relative to Salmonella) to the cytotoxins in these coal oils. This sensitivity, coupled with the low concentrations of mutagens relative to nonmutagenic cytotoxins in the coal oils, prevents exposure of the cells to concentrations of the mutagens in the mixtures that are high enough to be quantified in the CHO/ HG

ISSN:0192-2521    

DOI:10.1002/em.2860060405

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

年代:1984

数据来源: WILEY

摘要:

AbstractThe sister chromatid exchange (SCE) frequencies induced in bone marrow cells by in vivo irradiation with gamma rays before or after bromodeoxyuridine (Brdurd) incorporation were compared. The frequency of SCE at different postir‐radiation times was also measured in bone marrow cells in vivo, irradiated before Brdurd incorporation. Increased sensitivity to SCE induction by radiation was found in cells after Brdurd incorporation for one cycle when compared with cells irradiated before Brdurd incorporation. The increased SCE frequency persisted for at least 72 hr after the initial irradiation, implying that the gamma ray‐induced lesion(s) capable of eliciting an SCE are persistent and cannot be easily repai

ISSN:0192-2521    

DOI:10.1002/em.2860060406

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

年代:1984

数据来源: WILEY

摘要:

AbstractSeven promutagens belonging to two chemical classes—polycyclic aromatic hydrocarbons (PAHs) (benzo[a]pyrene, dimethyl benz[a]anthracene, 3‐methylcholanthrene, fluoranthene) and alkyl nitrosamines (dimethyl, diethyl, and dibutyl nitrosamine)—were studied in Chinese hamster ovary (CHO) cells. Findings of practical importance in the use of Aroclor 1254‐induced rat liver homogenate (S9) in the CHO/hypoxanthine‐guanine phosphoribosyl transferase (HGPRT) mutation assay were made. Our novel findings are (1) the inclusion of CaCl2in the S9 cofactor mixture dramatically decreased the cytotoxicity of S9, and (2) different S9 optimum concentrations were observed for structurally similar promutagens. The inclusion of CaCl2in the S9 cofactor mixture and the testing of each chemical of unknown S9 requirement at several S9 concentrations are therefore recommended for assaying promutagens in the CHO/HGPRT mutat

ISSN:0192-2521    

DOI:10.1002/em.2860060407

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

年代:1984

数据来源: WILEY

摘要:

AbstractIn theSalmonella/activation assay developed by Ames et al [1973, 1975] toxicity is not measured, though it is recognized by the loss of a cloudy appearance on the plate. One approach to the measurement of toxicity is described here and uses a microscope‐linked automated colony counter to estimate the number of micro‐colonies formed by histidine auxotrophs that stop growing after the depletion of histidine. This technique was used to evaluate the effect of toxicity on the revertant count for 16 mutagens, most of which were chosen because, from previous experience, their dose‐response curves manifested a maximum at an intermediate dose tested.One of the sixteen, 2‐nitrofluorene, was not toxic up to the maximum dose tested. The relationship between mutation and toxicity for the remaining fifteen allowed them to be grouped into two categories: (1) compounds that induced decreases in survival at the same dose at which the number of mutants decreased, and (2) compounds that induced toxicity, but survival was reduced at dose levels higher than those required to reduce the number of mutants. Possible explanations for this reduction of mutant counts occurring with little apparent concomitant increase in toxicity are examined. These results may be significant for attempts to estimate mutagenic potency and, to a lesser extent, construct mathematical models of the Am

ISSN:0192-2521    

DOI:10.1002/em.2860060408

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

年代:1984

数据来源: WILEY

摘要:

AbstractWe studied the effect of rat tissue extracts on induction of lambda prophage inEscherichia coli(λ) by L‐azaserine. Hepatic and pancreatic extracts, primarily the cytosolic fraction, markedly increased the rate of induction. Hepatic extracts from lipotrope‐deficient rats were somewhat more active than extracts from normal rats. The enhancing activity in normal rat hepatic cytosol was partially characterized. It reduced by about one‐half the dose of azaserine required for a given purpose. The enhancement was increased by preincubating the bacterial cells with cytosol; cells retained the effect after cytosol was removed. Enhancing activity was inhibited strongly by the amino acids phenylalanine, tryptophan, and tyrosine; to lesser extents by leucine, methionine, and serine; and not at all by proline or glutamine. It was eliminated by dialysis of the cytosol and reduced by omission of nicotinamide adenine dinucleotide phosphate (NADP) from the reaction mixture. Heating the cytosol to 60°C or 80°C or varying the pH of the reaction mixture from 6 to 8 had no significant effect. Treating the cytosol with trypsin appeared to release an inhibitor of the activity. Glutathione, cysteine, and β‐mercaptoethanol also enhanced X induction by azaserine, but the cytosolic activity was not affected by the thiol‐inactivating compound diethylmaleate (DEM). The results suggest that factors in cytosol interact with bacterial cells to facilitate transport of azaserine into the cells, primarily through the aromatic amino acid transport system. A small molecule, not a free thiol compound, appears to be involved. It may serve to establish reducing conditions protective for azaserine, the probable mechanism of action of sulthyd

ISSN:0192-2521    

DOI:10.1002/em.2860060409

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

年代:1984

数据来源: WILEY

摘要:

AbstractThe sister chromatid exchange (SCE) induction of mutagens with different mechanisms of action was comparatively investigated on permanent cell lines of the Chinese hamster (CHO, V‐79, and DON) with and without exogenous metabolic activation and with the use of various experimental protocols. CHO and V‐79 cells were treated with ethylmethanesulfonate (EMS), a direct mutagen; with the two indirect mutagens cyclophosphamide (CP) and benzo[a]pyrene (BP); as well as with the radical former hydrogen peroxide (H2O2) and hydroxyurea (HU), an inhibitor of DNA synthesis. Aside from an increased basal SCE level and a higher bromodeoxyuridine (Brdurd) sensitivity, there was no decisive difference betwen CHO and V‐79 cells. However, there was a distinct relationship between SCE induction and the experimental protocol used, which was most pronounced after HU treatment. Neither cell line was able to metabolize the indirect mutagen BP. Only in CHO cells did CP lead to increased SCE frequencies. However, in all cases, the simultaneous application of S9 mix produced a distinct SCE induction. In contrast, BP caused SCE induction in DON cells, whereas CP was not metabolized. The reason for these findings must obviously be sought in the metabolization of CP and BP via different monooxygenase systems, whose activity can differ in these permanent cell lines. One notable finding was that the number of SCE induced by H2O2could be distinctly reduced by the simultaneous application of S9 mix. This effect can be explained by the fact that S9 mix contains H2O2‐degrading enzymes. The results indicate that closely related cell lines differ in their capability for inducing SCE and that investigations of SCE inductions performed on only one cell line do not necessarily produce a representative r

ISSN:0192-2521    

DOI:10.1002/em.2860060410

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

年代:1984

数据来源: WILEY

摘要:

AbstractThe acetone extracts of ambient air particulates collected locally were tested for their capacity to induce sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) in human lymphocytes, and to induce gene mutations (GMs) inSalmonella typhimurium.The extracts caused dose‐related clastogenic/mutagenic responses in all three assay systems. With the same concentration, it seems that the AmesSalmonella/microsomal assay with TA98 gave the highest, and the chromosomal aberration assay with human lymphocytes the lowest, mutagenic/ clastogenic responses, respectively. Because high frequencies of SCEs were induced by solvent extracts of airborne particles, this study further indicated the usefulness of SCE assay in human lymphocytes for genotoxicity studies of airborne particle

ISSN:0192-2521    

DOI:10.1002/em.2860060411

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

年代:1984

数据来源: WILEY