摘要:

AbstractIn the search for relevant assays for mutagenicity testing, considerable attention has been given to the use of mammalian cells in vitro and the incorporation of metabolic activation in the protocol. Chinese hamster ovary (CHO) cells are commonly chosen as the target cells for cytogenetic tests because of their excellent growth characteristics and long lifespan in culture. However, there may be cellular factors affecting the uptake, metabolism, and repair of damage which are not the same in all cell lines. The response of CHO cells and three human diploid fibroblast strains (IMR‐90, WI‐38, S‐3299) to benzo(a)pyrene (BP) and dimethylnitrosamine (DMN) were compared using sister chromatid exchange (SCE) analysis as a measure of genetic damage. For both BP and DMN the human cells and the CHO cells showed dose‐response slopes that were significantly different from zero, except CHO cells treated with BP for 1 hr and S‐3299 cells treated with DMN. Whereas human and CHO cells showed similar dose‐responses to BP and the three human cell strains had similar dose‐responses to BP and DMN, the dose‐response of the human cells to DMN was statistically less significant than that of CHO cells. Reducing the duration of chemical treatment in CHO cells had no effect on the slope of the dose‐response curves for BP or DMN. The observed differences between human and CHO cells may reflect differences in the fate of metabolic int

ISSN:0192-2521    

DOI:10.1002/em.2860040302

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

年代:1982

数据来源: WILEY

摘要:

AbstractThe genotoxic activity of diesel exhaust emissions, particulate matter, and an organic extract of the particulate matter was evaluated in transplacentally exposed Syrian hamster fetal liver cells. The frequency of sister chromatid exchange (SCE) was determined on day 13 of gestation. The extract of diesel particulate matter caused a dose‐dependent increase in the frequency of SCE with a doubling in the incidence above 320mg/kg. The diesel particulate matter and diesel exhaust emissions did not alter the frequency of SCE. The extract and particulate matter did cause a dose‐dependent decrease in the mitotic activity of the fetal liver. The in utero SCE analysis was demonstrated to be a sensitive assay for determination of the genotoxic activity of a complex mixture in transplacentally exposed fetu

ISSN:0192-2521    

DOI:10.1002/em.2860040303

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

年代:1982

数据来源: WILEY

摘要:

AbstractThe effect of modifiers of liver mixed function oxidase activity on the in vitro α‐hydroxylation and mutagenicity of N‐nitrosopyrrolidine (NPYR) has been examined in rats and hamsters. Hamster post‐mitochondrial supernatants were able to convert NPYR to a mutagen more efficiently than rat preparations under all conditions studied. Aroclor 1254 pretreatment caused the greatest increase in mutagenic activity in both species while phenobarbital and 3‐methylcholanthrene pretreatment gave intermediate values when compared to uninduced preparations. Microsomal α‐hydroxylation of NPYR was induced by Aroclor 1254 pretreatment in both species. Pretreatment with 3‐methylcholanthrene increased α‐hydroxylation in hamsters but decreased it in rats. Phenobarbital pretreatment only slightly increased microsomal α‐hydroxylation in either species. When microsomal α‐hydroxylation rates were expressed per gram wet weight of liver, better agreement between rates of α‐hydroxylation and mutagenicity in phenobarbital pretreated animals was obtained since inducer associated changes in total microsomal protein content were taken into account. An example of differential induction of an activation pathway (α‐hydroxylation) and a degradative pathway (aldehyde dehydrogenase) is presented to illustrate a potential source of error in the interpretation of metabolic data obtained from post‐microsomal superna

ISSN:0192-2521    

DOI:10.1002/em.2860040304

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

年代:1982

数据来源: WILEY

摘要:

AbstractThe sperm abnormality‐inducing action of two potential mutagenic agents, mithramycin and triethylene melamine (TEM), in inbred Lakeview hamsters was studied and results compared with similar investigations in mouse. Test hamsters received subacute intraperitoneal exposures ranging from 0.01 to 0.25 mg/kg body weight with either agent for 5 consecutive days. Testis weights, epididymal sperm numbers, and body weights were also monitored at weeks 1, 4, and 10 after treatment. Mithramycin‐treated hamsters showed 21 times more sperm abnormalities than control (25% vs. 1.2%) whereas TEM elevated sperm abnormalities by eight fold. The frequency and type of aberrant sperm varied with dose and time, being the highest at weeks 1 or 4, rather than week 10, with either agent. Sperm number and testis weights remained depressed considerably from 4 to 10 weeks after treatment with either agent. Body weights in chemically treated hamsters remained within 28% of control for the test period. Even though our findings were in general agreement with those reported for mouse, the magnitude of the response and the stage of spermatogenic sensitivity in the chemical induction of sperm abnormalities in the two species were differ

ISSN:0192-2521    

DOI:10.1002/em.2860040305

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

年代:1982

数据来源: WILEY

摘要:

AbstractTo see if DNA crosslinks are involved in the induction of sister chromatid exchange (SCE), Chinese hamster ovary cells were exposed to two bifunctional alkylating agents, mitomycin C and 8‐methoxypsoralen, and their monofunctional derivatives, decarbamoyl mitomycin C and angelicin. The data indicate that monoadducts, rather than crosslinks, are responsible for SCE formation. Furthermore, all agents but angelicin produced short‐lived lesions that led to SCEs in the first period of DNA replication after treatment (twin SCEs), but not in the second (single SCEs). In contrast, angelicin, like methyl methanesulfonate and N‐acetoxyacetylaminofluorene, produced lesions that lasted more than one cycle, indicating that several different types of DNA lesions are capable of SCE indu

ISSN:0192-2521    

DOI:10.1002/em.2860040306

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

年代:1982

数据来源: WILEY

摘要:

AbstractThe presence of mutagenic nitro‐organic compounds on coal fly ash was indicated by the greatly reduced microbial mutagenicity of the ash filtrates with nitroreductase‐deficient strains of Salmonella typhimurium compared to their corresponding parental strains. Addition of the liver S‐9 microsomal enzyme preparation significantly increased the mutagenic activities of the ash extracts. Extracts of fly ash mutagens were prepared with horse serum, dimethyl sulfoxide, or azeotropic benzene/methanol mixture. The data were normalized to net revertants per 108Salmonella typhimurium cells per milligram of ash used. This normalization procedure is essential for interpretation of comparative results. Both four‐way and three‐way analyses of variance were used to simultaneously evaluate the differences between solvent extracts, fly ash mutagen, S‐9 activation, and nitroreductase‐deficient strains and their parental strains. Of the three extraction systems tested, benzene/methanol azeotropic mixture was generally found to have the highest extraction power, and horse serum was the lowest. The results show that overall 87.5% (± 1.8 SE) of the mutagenic activity of the fly ash was associated with nitro‐o

ISSN:0192-2521    

DOI:10.1002/em.2860040307

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

年代:1982

数据来源: WILEY

摘要:

AbstractAlthough actinomycin D (AMD) appears to cause chromatid breakage, it has been suggested that it merely weakens the chromosomal proteins, causing breaks to occur during the stress of fixation. To determine if this was true, we examined lymphocytes treated with AMD (3.5 μg/ml) for 90 min prior to harvesting for evidence of DNA repair. Besides single chromatid breaks, we observed a high frequency of chromatid exchange figures (translocations, inversions, rings) and closed isochromatid breaks, indicating that a type of DNA repair leading to chromosome aberrations had occurred prior to cell fixation. Therefore, at least some of the breaks observed after AMD treatment in G2represented true DNA damage and were not merely artifacts of fixation

ISSN:0192-2521    

DOI:10.1002/em.2860040308

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

年代:1982

数据来源: WILEY

摘要:

AbstractSister chromatid exchange (SCE) induction by the procarcinogen benzo (a)‐pyrene (BP) was studied using two established cell lines. Chinese hamster ovary (CHO) and Chinese hamster lung (Don) cells were exposed to varying concentrations of BP in the presence and absence of a rat liver metabolizing system. Results showed a significant difference in the abilities of the two cell lines to induce SCE in the absence of liver homogenate. These experiments demonstrate that Don cells are capable of generating active metabolites from biologically inactive procarcinogens presumably due to an inherent metabolizing system which is deficient or absent in CHO cell

ISSN:0192-2521    

DOI:10.1002/em.2860040309

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

年代:1982

数据来源: WILEY

摘要:

AbstractA series of methylated metabolites of the flame retardant tris(2,3‐dibromopropyl) phosphate (Tris‐BP) were tested for mutagenicity in Salmonella, along with the parent chemical and other structurally related chemicals. The metabolites produced a gradient of mutagenic responses in TA1535 in the same dose range and up to the same magnitude as the Tris‐BP response. None of the metabolites tested appeared to be the ultimate mutagen, since they all required S‐9 for their mutagenic a

ISSN:0192-2521    

DOI:10.1002/em.2860040310

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

年代:1982

数据来源: WILEY

摘要:

AbstractThe dose‐response for the induction of acentric chromosome fragments was determined in neuroblasts of the grasshopper embryo (Chortophaga viridifasciata De Geer, Orthoptera: Acrididae) exposed in vitro to four direct‐acting chemicals known to be mutagenic, clastogenic, and carcinogenic: 4‐nitroquinoline‐1‐oxide (4NQO), N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG), Adriamycin (ADM), and bleomycin (BLM). After a 1‐hr exposure followed by a 3‐hr recovery period (untreated cell cycle time is 4 hr), acentric fragments were observed at doses down to 1 μM 4NQO, 1.25 μM M MNNG, and 0.125 μM ADM and BLM. After an 8‐hr continuous exposure, acentric fragments were induced by 4NQO at a dose as low as 0.125 μM. These low concentrations also reduced the number of dividing cells. No chromosome aberrations or mitotic effects were observed in untreated embryos or in those exposed only to the solvent dimethyl sulfoxide.Because of the short cell cycle and the sensitivity of the neuroblast to the induction of acentric chromosome fragments by chemical clastogens, a minimum of time is needed to perform the test. From a comparison with the prominent clastogen test systems currently used, it is concluded that the grasshopper neuroblast test is the fastest and that it detects some agents that some systems do not. Grasshoppers have a worldwide distribution. If neuroblasts of other species prove to be as sensitive to mutagens as those of Chortophaga, investigators in many countries would have available a eukaryotic mutagen test system that is simple, fast

ISSN:0192-2521    

DOI:10.1002/em.2860040311

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

年代:1982

数据来源: WILEY