ISSN:0192-2521    

DOI:10.1002/em.2860050602

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

年代:1983

数据来源: WILEY

ISSN:0192-2521    

DOI:10.1002/em.2860050603

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

年代:1983

数据来源: WILEY

摘要:

AbstractChinese hamster ovary (CHO) cells were grown on hydrated collagen gels, the overlaying medium removed leaving the cells at an air/collagen interface, and the cells exposed to a dynamic flow of ethylene oxide. Increases in CHO cell mutant frequency and decreases in cell viability were observed. To establish if the exposure system could be simplified, cells were exposed in sealed bottles (static system) to ethylene oxide. No substantial changes in cytotoxicity, mutant frequency, or effective concentration were noted when comparing static versus dynamic exposure systems. The general usefulness of the exposure system using cells grown on collagen gels was evaluated in a static system using propylene oxide and 1,2‐dichloroethane, both of which were found to be mutagenic and cytotoxic. Comparatively, the exposure of cells by the collagen gel method was as effective in detecting genotoxic damage as were conventional methods (cells covered with medium) using cells grown on glass substrates. The exposure of CHO cells on collagen gels to highly volatile mutagens was simple and inexpensive, and may be generally useful in the detection of gaseous or volatile mutagen

ISSN:0192-2521    

DOI:10.1002/em.2860050604

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

年代:1983

数据来源: WILEY

摘要:

AbstractA group of 45 monosubstituted aniline compounds was tested for the induction of point mutations in Salmonella typhimurium and Escherichia coli as well as for unscheduled DNA synthesis (UDS) in rat hepatocyte culture. Eleven compounds were bacterial mutagens, and five compounds induced UDS. Among these a correspondence between mutagenicity and UDS occurred for only two compounds (o‐phenylenediamine and 4‐aminobiphenyl), and these were also reported to be carcinogenic in rodents. Bacterial mutation was observed for one compound (p‐phenylenediamine) not carcinogenic in rodents, and six suspect carcinogens were not detected in either test. In addition, eight compounds of unknown carcinogenic potential induced either bacterial mutation o

ISSN:0192-2521    

DOI:10.1002/em.2860050605

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

年代:1983

数据来源: WILEY

摘要:

AbstractStreptonigrin (NSC‐45383), a direct‐acting clastogen which induces SCEs in vivo and chromosome aberrations both in vivo and in vitro, was evaluated for SCE induction in both G0and stimulated rabbit lymphocytes. Determinations were made for 16 cultures from seven female rabbits. These included controls as well as cells exposed to 90 μg/kg in vivo, cells pulse‐treated with 50 ng/ml in vitro, and a culture continuously exposed to 5 ng/ml in vitro. For all cultures the SCE/ cell frequency was determined from 20 complete (44 chromosome) metaphases and, in selected cultures, SCEs on individual chromosomes (880 per culture from 20 cells) were enumerated to determine SCE/chromosome frequency and the chromosomal distribution of SCEs. Analysis of variance and least significant difference tests of the √x transformed SCE/cell data show that cells exposed to Streptonigrin while dividing have significantly higher (P<0.01) frequencies (over double the control 5.3 SCE/cell value) whereas treated G0cells were not significantly different from the controls. Dispersion analysis of both SCE/cell and SCE/ chromosome data confirms the adequacy of the Poisson distribution for spontaneous or baseline but not streptonigrin‐in

ISSN:0192-2521    

DOI:10.1002/em.2860050606

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

年代:1983

数据来源: WILEY

摘要:

AbstractAdministration of cyclophosphamide (5, 10, 20 and 25 mg/kg body weight) to male CD‐I mice 2 hr after subcutaneous implantation of a 5‐bromo‐2′‐deoxyuridine (BrdUrd) pellet (55 mg) resulted in a dose‐dependent increase in sister chromatid exchanges (SCE) in bone marrow cells. Treatment with cyclophosphamide (15 mg/kg body weight) at the time of BrdUrd implantation and 2, 6.5, and 13 hr post‐BrdUrd implantation resulted in the induction of approximately 19 SCE/cell indicating that the bone marrow SCE response was independent of the time of administration. Treatment with cyclophosphamide (15 mg/kg body weight) at 26, 19, 13, and 6 hr prior to BrdUrd implantation resulted in baseline SCE (3.3 SCE/cell) at 26 hr with an increasing number of SCE/cell with decreasing time prior to BrdUrd implantation.These results compare favorably with those obtained by Kram et al [1981] with mitomycin C (MMC) using a similar protocol. The time‐dependent induction of SCE is qualitatively similar for CP and MMC, both of which are bifunctional alkylating agents metabolically activated by oxidation and reduction, respectively, and suggests that these two compounds may induce SCE by a si

ISSN:0192-2521    

DOI:10.1002/em.2860050607

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

年代:1983

数据来源: WILEY

摘要:

AbstractCommercial preparation of fungicides (captan and maneb), herbicides (bromacil, paraquat, picloram, and 2,4‐D), and insecticides (carbaryl, chlorpyrifos, dimethoate, DDT, diazinon, carbofuran, and permethrin) were tested for their ability to induce complete and partial chromosome losses in Drosophila melanogaster males. In an attempt to identify the mutagenic activity of pesticides that are toxic in low concentrations in Drosophila, these males were mated with mus‐302 repair‐defective females. The rationale for this mating scheme is based on the repair of genetic damage in Drosophila sperm by maternal enzymes in the zygote, and on the reports that there may be increases in the frequency of recovery of chemically induced chromosome losses in crosses of treated males with mus‐302 females. Verification of the sensitivity of this screen in this study came from significant increases in the frequency of chromosome loss induced by low concentrations of the positive controls. N‐nitrosodimethylamine and methyl methanesulfonate. Of the 13 pesticides, the insecticide chlorpyrifos induced a significant amount of ring‐X chromosome loss. No pesticide induced a significant increase in partial chromosome loss. These results are discussed in relation to the usefulness of repair‐defective mutants in screens for genetic damage in Drosophila and other higher eukaryotes by chemicals that are toxic or cause sterility at low c

ISSN:0192-2521    

DOI:10.1002/em.2860050608

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

年代:1983

数据来源: WILEY

摘要:

AbstractTuberculosis patients under therapy with the drug combination isoniazid (INH) and para‐aminosalicylic acid (PAS) were screened to investigate the cytogenetic effects. Results were compared with those from the patient controls (ie, tuberculosis patients before starting drug therapy) and general controls (individuals from the general population). The induction of chromosome aberrations was homogeneous and increased significantly in all the drug‐exposed patients, whereas the frequency of sister chromatid exchanges (SCEs) was increased only in one of them. These results indicated differences in the two processes: chromosome aberrations and SCEs. Patients under therapy exhibited no change in cell growth kinetics, but the mitotic index was slightly enhanced compared to patient controls. It is concluded that the drug combination of INH+PAS induces damage in lymphocyte chromosomes in vivo. Further studies should be carried out on germ ce

ISSN:0192-2521    

DOI:10.1002/em.2860050609

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

年代:1983

数据来源: WILEY

摘要:

AbstractBenzo(ghi)perylene (B(ghi))Per, (191–24–2)) and coronene (Cor, (191–07–1)) are major constituents of the polycyclic aromatic hydrocarbons (PAH) found in automobile exhaust and polluted air [eg, Grimmer et al, 1981]. Nitration of these PAH by NO2and traces of HNO3, which are also formed in automobile exhaust, seems highly probable. To identify the presence of these nitroarenes in environmental samples and to examine their mutagenic potencies we synthesized and characterized nitro derivatives of both PAH. 5‐NO2B(ghi)Per (81316‐87‐2) and l‐NO2Cor (81316‐84‐9) produced 405 and 340 revertants/nmole respectively in TA98 in the presence of 0.6 mg of microsomal enzymes (S‐9) per plate in the Ames test. 5,8‐diNO2B(ghi)Per (83292‐25‐5) and 5,10‐diNO2B(ghi)Per (83292‐26‐6) produced 21,500 and 4,000 revertants/nmole in TA98 without microsomal activation. Mutagenicity for the dinitrobenzo(ghi)perylenes was also high in TA98NR and TA97 but was reduced by 97% in TA98‐1,8DNP. There is close similarity in the orientation and distances between reactive sites (nitrenium ion and carbocation) on the dinitrobenzo(ghi)perylenes and 1,6‐dinitropyrene (42397‐6

ISSN:0192-2521    

DOI:10.1002/em.2860050610

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

年代:1983

数据来源: WILEY

摘要:

AbstractThe mutagenic responses of 12 anticancer drugs—lomustine, dacarbazine, mitomycin C, chlorambucil, cis‐diamminedichloroplatinum (II), busulfan, ellipticine, daunomycin, adriamycin, VM‐26, VP16‐213, and bleomycin—in Chinese hamster ovary (CHO) cells at two independent genetic loci which affect purine salvage pathway enzymes, hypoxanthine‐guanine phosphoribosyl transferase (HGPRT) and adenosine kinase (AK) have been compared within the same experiments. The cellular mutants which lack either HGPRT (HGPRT−mutants) or AK (AK−mutants) activity can be directly selected in CHO cells using 6‐thioguanine and 6‐methyl mercaptopurineriboside (6‐MeMPR) respectively, and optimal conditions for their selection have been described. Results of our studies show that all of the above drugs caused a concentration‐dependent increase in the frequencies of both 6‐thioguanine‐ and 6‐MeMPR‐resistant mutants. However, for a number of these drugs, namely adriamycin, daunomycin, bleomycin, and dacarbazine, which are only weakly mutagenic at the HGPRT locus, a relatively strong and clear mutagenic response was observed at the AK locus. In contrast, VM‐26 showed a more pronounced effect at the HGPRT locus. For the remaining compounds, the mutagenic responses of the two loci (as indicated by the slopes of the dose‐response curves) were comparable. The observed increase in the frequency of AK−mutants after treatment with various drugs, many of which predominantly induce frameshift and chromosome‐breakage type of genetic lesions, suggests that like the HGPRT locus the AK locus is also capable of detecting all the different types of genetic lesions. The favorable response of the AK locus as compared to that of HGPRT locus in these studies indicates that the selection system of AK−mutants should provide a very useful genetic ma

ISSN:0192-2521    

DOI:10.1002/em.2860050611

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

年代:1983

数据来源: WILEY