ISSN:0192-2521    

DOI:10.1002/em.2860120402

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.2860120403

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

年代:1988

数据来源: WILEY

摘要:

AbstractTetracycline and chloramphenicol increase the number of mutant colonies of strain TA102, which carries the reverting gene on die plasmid pAQ1. Determination of the plasmid content by agarose gel analysis shows that the increase of the mutant colony number is paralleled closely by an increase of die number of pAQ1 plasmids per cell, indicating mat the two compounds do not increase the frequency of mutants “per gene,” but only enhance the number of the genes at which mutations can occur. Thus, not considering die molecular processes could result in mistakenly attributing the increase in the number of mutants per plate (respective to the number of mutants per cell) to a mutagenic activity of die antibiot

ISSN:0192-2521    

DOI:10.1002/em.2860120404

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

年代:1988

数据来源: WILEY

摘要:

AbstractThe human carcinogen and nitrogen mustard chlornaphazine (CN) has been confirmed to be mutagenic toSalmonellaand, unexpectedly, the more so when evaluated in the presence of liver S9 mix. It also has been established as clastogenic to Chinese hamster lung cells exposed in vitro to dose levels>2.5 μg/ml. Chlornaphazine subdued mice at doses of 5 g/kg, but only the occasional death occurred during the 4 days following oral administration of this dose in com oil. Consequently, a median lethal dose level was not established. Nonetheless, dose levels of 500 mg/kg or greater gave a clear positive response in both the mouse and the rat bone marrow micronucleus assay. Although depression of erythropoeisis was observed in mice, a clastogenic response still was observed in the bone marrow 24 hr after dosing. The positive response in the rat was greater than that observed in the mouse. The present data provide a further instance of an established human carcinogen being readily detected by standard in vitro and in vivo mutagenicity assays

ISSN:0192-2521    

DOI:10.1002/em.2860120405

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

年代:1988

数据来源: WILEY

摘要:

AbstractUsing an improved microculture method, we investigated how the patterns of persistence of urethane‐induced SCEs in lymphocytes differ among individuals and strains of mice (the ddY and C57BL strains), and we attempted to speculate on their relationship to carcinogen susceptibility. After a single intraperitoneal (i.p.) injection of 900 mg/kg of body weight of urethane into ten female mice each for the two strains, blood samples for the SCE analysis were collected from the tail vein at ten times during the 180 posttreatment days for each individual. Immediately after the treatment, SCE values increased to about three to four times the spontaneous values in all of the animals tested and then fell gradually. (The difference from spontaneous values was statistically significant until 120 days after the treatment.) Even after 180 days, however, some “outlier” cells with exceptionally high SCEs (>20) persisted. Although there was some difference in average SCEs between the ddY and C57BL strains, the magnitude of the difference was too small to account for the difference between the strains in the incidence of urethane‐induced malignancy. Also, when autopsy data at the 200th posttreatment day were matched individually with the data of SCE values within each strain, it was difficult to predict the individual risk of the occurrence of lung adenoma or other tumors from the relative difference in SCE

ISSN:0192-2521    

DOI:10.1002/em.2860120406

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

年代:1988

数据来源: WILEY

摘要:

AbstractExtract of particulate matter (EPM) from gasoline engine exhaust has been investigated for cytotoxic and genotoxic effects in the concentration range 0.16‐10 μg/ml by means of short‐term bioassays using mammalian cell culture systems. Cytotoxicity is demonstrated by a strong dose‐dependent reduction of cloning efficiency after treatment of V79 cells with EPM. Employing the dye exclusion test with erythrosin B, no considerable loss of cell viability was observed. Using the same cell system, EPM revealed a highly increased number of aberrant mitoses, whereby the occurrence of C mitoses and metaphases with chromosome clusters was especially pronounced. This effect led to mitotic arrest as shown by a highly increased mitotic index at 5 and 10 μg/ml EPM. The results indicate disturbances of the mitotic spindle in a way similar to the known spindle poison colcemid. As a consequence of spindle disturbances, EPM produced numerical chromosome alterations such as aneuploidy and polyploidy. Cytogenetic analyses using human lymphocyte cultures treated with EPM revealed a slight increase of chromosomal aberrations at 10 μg/ml and a dose‐dependent induction of sister chromatid exchanges in the range 2.5‐10 μg/ml. At least, EPM showed a dose‐dependent increase in the cell transformation assay using SV 40‐infected Syrian hamster kidney cultures. The great variety of cytotoxic and genotoxic effects found with EPM suggests a potential health hazard to human populations exposed to gasoline engine exhaust. The possible contribution to cytotoxic and genotoxic activity by organolead compounds derived from antiknock addit

ISSN:0192-2521    

DOI:10.1002/em.2860120407

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

年代:1988

数据来源: WILEY

摘要:

AbstractThe ability of nitrilotriacetic acid (NTA) to induce aneuploidy was studied in the germ line of bothDrosophilaand the mouse. The Free Inverted × Chromosomes (FIX) genetic system, adopting a brooding scheme, was used to detect induced aneuploidy inDrosophila, and a cytogenetic method based on chromosomal counting in secondary spermatocytes was used in the mouse.InDrosophilaa highly significant (P<0.001) increase of aneuploidies was produced by NTA (5 × 10−2M), which was greater than that produced by colchicine (7.5 × 10−6M) and 5‐fluorodeoxyuridine (10−4M), which were used as positive controls. Brooding effects were observed with NTA, which produced a maximum induction of chromosomal gain in brood I, suggesting a possible stage‐specific action during meiosis. The ability of NTA (275 mg/kg body weight) to induce meiotic aneuploidy (hyperhaploidy) also was confirmed in the mouse (P<0.001), where all the aneuploidies detected were attributable to treatment of the metap

ISSN:0192-2521    

DOI:10.1002/em.2860120408

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

年代:1988

数据来源: WILEY

摘要:

AbstractHuman cytomegalovirus (CMV) is potentially an effective but often overlooked genotoxic agent in humans. We report here evidence that indicates that infection by CMV can induce chromosome alterations and mitotic inhibition. The frequency of chromosome aberrations induced was dependent on the input multiplicity of infection (m.o.i.) for human lung fibroblasts (LU), but not for human peripheral blood lymphocytes (PBLs) when both cell types were infected at the GO phase of the cell cycle. The aberrations induced by CMV were mostly chromatid breaks and chromosome pulverizations that resembled prematurely condensed S‐phase chromatin. Pulverized chromosomes were not observed in LU cells infected with virus stocks that had been rendered nonlytic by UV‐irradiation at 24,000 ergs/mm2or from infection of human lymphocytes. In LU cells infected with UV‐irradiated CMV, the frequency of aberrations induced was inversely dependent on the extent of the exposure of the CMV stock to the UV‐light. In permisive CMV infection of proliferating LU cells at 24 hr after subculture, a high percentage (>40%) of the metaphase cells were arrested at their first metaphase and displayed severely condensed chromosomes when harvested 48 hr later. A significant increase (p<0.05) in the chromosome aberration frequency was also observed. Our study shows that CMV infection is genotoxic to host cells. The types and extent of damage are dependent on the viral genome expression and on the cell cycle stage of the cells at the time of infection. The possible mechanisms for induction of chromosome damage by CMV are di

ISSN:0192-2521    

DOI:10.1002/em.2860120409

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

年代:1988

数据来源: WILEY

摘要:

AbstractTwo tricyclic antidepressants, amitriptyline and imipramine, were evaluated for their in vitro cytogenetic effects in human lymphocyte cultures.Peripheral blood cultures from three normal healthy donors were set up for 72 hr for each of the drugs. The drugs were added at the start (72‐hr exposure), 24 hr (48‐hr exposure), and 48 hr (24‐hr exposure) after initiation of the cultures. The concentrations evaluated at each exposure time were 50, 250, 1,000, and 10,000 ng/ml for amitriptyline and 25, 500, and 5,000 ng/ml for imipramine. The first two concentrations correspond to the plasma levels of the respective drugs after therapeutic doses. All treatments for a donor were given at the same time. Untreated cultures served as controls for the baseline frequency of the parameters assayed. The parameters assayed were chromosome aberrations, mitotic index, and sister chromatid exchanges (SCEs).Amitriptyline was found to be nongenotoxic at plasma levels by all the parameters assayed. However, frequencies of chromosome aberrations and SCEs were significantly increased at concentrations 4 and 40 times the plasma level (1,000 and 10,000 ng/ml) although the actual increase was small. The mitotic index was not affected at any concentration.Though imipramine showed a significant increase in chromosome damage at the upper plasma level and at concentrations higher than that, SCE frequency was significantly increased only at concentration higher than the plasma level (5,000 ng/ml), the actual increase being small for both these parameters. The mitotic index was not affected at any concentration.These results suggest mat amitriptyline may be a slightly safer drug than imipramine from a genetic point of

ISSN:0192-2521    

DOI:10.1002/em.2860120410

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.2860120411

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

年代:1988

数据来源: WILEY