摘要:

AbstractWe show that for the in vitro cytochalasin‐B human lymphocyte micronucleus (MN) test, the quantification of the DNA content of MN and the difference in DNA content between the two macronuclei in the binucleate cells without MN, as measured by image analysis, gives a first estimation of the aneugenic potential of a test compound. Cultures of isolated human lymphocytes were exposed either to γ‐rays as a clastogen or to carbendazim (MBC) as an an‐eugen. The lymphocytes were stained with Feulgen stain and the MN were analyzed for DNA content with a Magiscan 2A image analyzer. The mean DNA content of MN induced by MBC were statistically higher than γ‐irradiation‐induced MN. It was demonstrated that in culture the lymphocytes, as well as the MN, are in different stages of the cell cycle, but this will not affect the discriminating power of the MN DNA content when only G1 cells are considered, or when DNA content of the MN is expressed relative to the total genome. The identification of Gl and G2 cell populations from image analysis data was performed by extrapolation of DNA content data from Gl‐ and G2‐sorted lymphocytes with a FacStar plus flow sorter. It was demonstrated that in MBC‐treated cells the DNA rearrangement between the macronuclei in binucle‐ates without MN was on the average higher than in γ‐irradiated and untreated cells, which points to aneugenic effects of MBC without the formation of MN. In contrast to DNA content measurements, the area of the MN is not a reliable measure for discriminating clastogens from aneugens.

ISSN:0893-6692    

DOI:10.1002/em.2850250402

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

年代:1995

数据来源: WILEY

摘要:

AbstractAlthough individuals who abuse drugs are prone to an increased risk of malignancy, the mutagenic and carcinogenic potential of these agents has received relatively little attention. We report here on the potential of morphine to induce micronuclei in murine lymphocytes. Following a single intraperitoneal injection of 20 mg/kg morphine, the frequency of micronucleated binuclear (cytochalasin‐blocked) murine T‐ and B‐splenocytes was elevated from 1 2–36 hr after treatment. The maximum frequencies seen 24 hr after injection were 6.3– and 4.9–fold greater than the respective controls. A dose‐dependent induction of micronuclei was observed from 5–20 mg/kg morphine, with no further increases in frequency produced by higher doses. In contrast, incubation of mitogen‐stimulated splenocytes with 10‐7‐10‐4M morphine in vitro produced no change in frequency of micronucleated cells relative to controls. Treatment with the narcotic antagonist naloxone (5 mg/kg) alone had no effect on the frequency of micronuclei, but reduced the clasto‐genic response of a subsequently administered dose of morphine (20 mg/kg). Thus, in murine lymphocytes morphine indirectly produces genetic damage, which is at least in part opioid receptor‐media

ISSN:0893-6692    

DOI:10.1002/em.2850250403

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe mutagenicity of chlorinated humic drinking waters is accounted for mainly by a single contaminant, 3‐chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2(5H)‐furanone (MX), as assessed inSalmonella typhimuriumstrain TA100. In the present study, 3,4‐dichl‐oro‐5‐hydroxy‐2(5H)‐furanone (mucochloric acid, MA), another drinking water contaminant much less potent as a mutagen in TA100 than MX, was tested in Chinese hamster ovary (CHO) cells for the induction of mutation at the hypoxanthine phosphoribosyl transferase (hprl) locus to 6‐thioguanine resistance (TG'). Unexpectedly, MA induced TG mutants in CHO cells with a potency comparable to that reported previously for MX. In subsequent experiments withS. typhimurium, the presence of pKM1O1 plasmid in strain TA100 increased susceptibility to the mutagenicity of MA, but much less than to that of MX, relative to the parental strain TA1535 lacking pKMlOl. The difference between the two compounds in TA100 thus appears to be due to a higher enhancement of the mutagenicity of MX than that of MA by pKM101 mediated error‐prone DNA r

ISSN:0893-6692    

DOI:10.1002/em.2850250404

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

年代:1995

数据来源: WILEY

摘要:

AbstractTwo arsenic compounds, sodium arsenite (NaAsO2) and sodium arsenate (Na2HAsO4), were tested for their possible genotoxicity in germinal and somatic cells ofDrosophila melanogaster.For germinal cells, the sex‐linked recessive lethal test (SLRLT) and the sex chromosome loss test (SCLT) were used. In both tests, a brood scheme of 2–3–3 days was employed. Two routes of administration were used for the SLRLT: adult male injection (0.38, 0.77 mM for sodium arsenite; and 0.54, 1.08 mM for sodium arsenate) and larval feeding (0.008, 0.01, 0.02 mM for sodium arsenite; and 0.01, 0.02 mM for sodium arsenate). For the SCLT the compounds were injected into males. Controls were treated with a solution of 5% sucrose which was employed as solvent. The somatic mutation and recombination test (SMART) was run in thew+/weye assay as well as in themwh+/+flr3wing test, employing the standard and insecticide‐resistant strains. In both tests, third instar larvae were treated for 6 hr with sodium arsenite (0.38, 0.77, 1.15 mM), and sodium arsenate (0.54, 1.34, 2.69 mM). In the SLRLT, both compounds were positive, but they were negative in the SCLT. The genotoxicity of both compounds was localized mainly in somatic cells, in agreement with reports on the carcinogenic potential of arsenical compounds. Sodium arsenite was an order of magnitude more toxic and mutagenic than sodium arsenate. This study confirms the reliability of the Drosophila in vivo system to test the genotoxicity of environmental compounds. © 1995 Wiley

ISSN:0893-6692    

DOI:10.1002/em.2850250405

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

年代:1995

数据来源: WILEY

ISSN:0893-6692    

DOI:10.1002/em.2850250406

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

年代:1995

数据来源: WILEY

摘要:

AbstractTests for the induction of chromosomal aberrations (ABS) and micronuclei (MN) in bone marrow cells of mice have been conducted on 65 chemicals. Although these tests were not conducted with the purpose of comparing the outcomes of these two in vivo genetic toxicity end‐points, the availability of these test results permits such a comparison. Based on studies to date, results from the 2 tests agree for more than 80% of the chemicals; 17 gave positive results in both tests, and 36 gave negative results in both. Seven chemicals were positive only for ABS and 5 were positive only for MN. Three chemicals that were originally concluded to be positive for ABS but not for MN were found to induce MN when the MN protocol was modified to more closely reflect the ABS protocol. Among the 12 chemicals for which there are discrepant results, there are only 2 for which the difference is convincing. One of these, selenium sulfide (MN negative, ABS positive) remains an enigma; further studies are being conducted. The second, isoprene (MN positive, ABS negative) will be difficult to pursue because the studies reported here were done by inhalation exposure. Based on the outcomes of these comparisons, protocol factors, rather than endpoint specificity, appear to be the major source of discrepant test results. Thus, these results do not support a recommendation that both tests be conducted in a primary testing scheme for genetic toxicity. © 1995 Wiley‐Liss, IncThis article is a US Government work and, as such, i s in the public domain in the United States of Amer

ISSN:0893-6692    

DOI:10.1002/em.2850250407

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

年代:1995

数据来源: WILEY

摘要:

AbstractSimultaneous assessment of in vivo micronucleus and chromosome aberration endpoints has been described in the rat and the mouse. Bone marrow and spleen cells were utilized for genotoxicity assessment. A cellulose column methodology was used in the micronucleus assay (where applicable) to eliminate nucleated cells and facilitate cytogenetic scoring. The test agents–cyclophosphamide, chlorambucil, and acrylamide–produced qualitatively comparable results between micronucleus and chromosome aberration endpoints and varied slightly on a quantitative basis depending on the type of test agent and tissue studied. The results from test agents such as cyclophosphamide, chlorambucil, acrylamide, dimethylnitrosamine, vincristine, and x‐rays indicated that bone marrow cytogenetic results are similar to spleen and that the spleen tissue is at least as sensitive as the bone marrow. The concurrent analysis of cytogenetic damage in vivo using a multiple endpoint‐multiple tissue approach described here has the following advantages: a) reducing the overall animal usage, b) clarifying marginal micronucleus and/or chromosome aberration data, c) correlating cytogenetic results from multiple endpoints and multiple tissues, and d) helping the investigation of the mechanism of action of test agents and their potential target organs. Also, the multiple endpoint‐multiple tissue approach can be extended to other endpoints, tissues, and species (where appropriate and practical) to obtain detailed genotoxicity information. © 1995 Wiley

ISSN:0893-6692    

DOI:10.1002/em.2850250408

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

年代:1995

数据来源: WILEY

ISSN:0893-6692    

DOI:10.1002/em.2850250409

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

年代:1995

数据来源: WILEY

ISSN:0893-6692    

DOI:10.1002/em.2850250410

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

年代:1995

数据来源: WILEY

ISSN:0893-6692    

DOI:10.1002/em.2850250411

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

年代:1995

数据来源: WILEY