ISSN:0893-6692    

DOI:10.1002/em.2850210102

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

年代:1993

数据来源: WILEY

摘要:

AbstractSeveral Japanese agencies are required to perform mutagenicity tests according to regulatory guidelines. Although each agency's guidelines address a specific purpose, the experimental principles behind them are similar, and general methodological recommendations have been issued by the Ministry of Agriculture, Forestry, and Fisheries [1985]; Ministry of Health and Welfare [1990]; Ministry of Labor [1991]; and Ministry of Health and Welfare [1992]. Four major guidelines for mutagenicity testing in Japan and some amendments are briefly introduced. In addition, several procedures in Japanese guidelines that differ from those of other countries or organizations are discussed. © 1993 Wiley‐Liss, Inc. © 1993 Wiley‐Liss

ISSN:0893-6692    

DOI:10.1002/em.2850210103

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

年代:1993

数据来源: WILEY

摘要:

AbstractThis work presents genetic toxicology testing requirements in three industry sectors; pharmaceuticals, pesticides, and industrial chemicals. © 1993 Wiley‐Liss, I

ISSN:0893-6692    

DOI:10.1002/em.2850210104

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

年代:1993

数据来源: WILEY

ISSN:0893-6692    

DOI:10.1002/em.2850210105

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

年代:1993

数据来源: WILEY

摘要:

AbstractNew requirement for chemicals subject to mutagenicity testing from the U.S. Environmental Protection Agency (USEPA) are discussed. Also detailed are two categories in the 1986 Mutagenicity Risk Assessment Guidelines. © 1993 Wiley‐Liss, I

ISSN:0893-6692    

DOI:10.1002/em.2850210106

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

年代:1993

数据来源: WILEY

ISSN:0893-6692    

DOI:10.1002/em.2850210107

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

年代:1993

数据来源: WILEY

摘要:

AbstractA series of experiments was conducted in which Chinese hamsters inhaled PAN, an ubiquitous pollutant that is present in the atmosphere at concentrations that are as high as, or higher than, other known genotoxic agents. The animals were exposed to PAN in air at concentrations of = 3 ppm for up to 1 month and then examined for somatic mutations and chromosomal aberrations. Mutations were assayed by measuring the frequency of thioguanine‐resistant lung fibroblasts (isolated de novo and cultured). Chromosomal aberrations were assayed by measuring the frequency of micronuclei in either the bone marrow (polychromatic erythrocytes) or the lungs (binucleate lung fibroblasts cultured in the presence of cytochalasin B). The results for the test animals were compared to those from animals exposed similarly, but without PAN. Although in each experiment the mutation frequencies for the test animals were higher than the corresponding controls, the mutation frequencies were not significantly different from the concurrent negative controls (P>.05) or the historical controls, except for experiment C. In experiment C, there was a significant regression of mutation frequency versus dose (P<0.001) if all of the historical controls for pooled animals are included at zero dose. No reproducible evidence of chromosomal breakage was found in either lung or bone marrow. Thus, although PAN has been found to be a bacterial mutagen, we did not find statistically significant evidence of mutagenicity in vivo. The toxicity of PAN limited the exposure concentration that could be used. When all of the PAN data were used, the best estimate of the mutagenic potency proved to be comparable to that of ethylene dibromide, a carcinogenic atmospheric pollutant. © 1993 Wiley‐Liss,

ISSN:0893-6692    

DOI:10.1002/em.2850210108

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

年代:1993

数据来源: WILEY

摘要:

AbstractAminoglycosides are a class of antibiotics that interfere with protein translation. Geneticin and hygromycin are two such agents, which have been shown to exhibit highly toxic effects in mammalian cells. Cloned bacterial genes, which inactivate these antibiotics, have facilitated the establishment of dominant selection systems, which are widely used in eukaryotic molecular genetics. We have examined the effect of aminoglycosides on the sister chromatid exchange (SCE) frequency in transformed human fibroblast cell lines. Geneticin and hygromycin were both found to increase SCE frequency in all cell lines examined, including a cell line derived from a patient with Bloom syndrome, a disorder exhibiting an elevated spontaneous SCE frequency. Induction was seen to occur in a dose‐responsive manner and was also observed in cells expressing the resistance genes that inactivate the cellular toxicity of these antibiotics. The implications of these findings for somatic cell genetics and for human gene therapy protocols are discussed. © 1993 Wiley‐Liss,

ISSN:0893-6692    

DOI:10.1002/em.2850210109

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

年代:1993

数据来源: WILEY

摘要:

AbstractConcomitant to a developmental toxicology study of selenium in long‐tailed macaques (Macaca fascicularis), a transplacental bone marrow micronucleus assay was conducted in the fetuses of treated animals. Selenium was administered as L‐selenomethionine by nasogastric intubation at 0, 150 or 300 μg/kg‐day to pregnant macaques daily throughout organogenesis (gestation days 20–50). Pregnancy was terminated on gestation day 100 ± 2 and fetuses were obtained by hysterotomy. Selenium concentrations in maternal blood were monitored throughout pregnancy and selenium concentrations in fetal blood were measured at hysterotomy. Maternal circulating selenium did not exceed 4 ppm in plasma or 3.7 ppm in erythrocytes. Selenium in cord blood was ≤ 0.1 ppm in plasma and ≤ 1.1 ppm in erythrocytes at 300 μg/kg‐day. Fetal bone marrow smears were prepared from the humerus and micronucleated polychromatic erythrocytes were scored. No increase of micronucleus frequency was detected in any dose group, although signs of maternal selenosis were obvious. This finding is compared to the previous observation that micronuclei were induced in the bone marrow of adult nonpregnant macaques treated at 600 μg/kg‐day, a lethal dose yielding blood selenium levels to 7.3 ppm in plasma and 5.7 ppm in erythrocytes after 15 days of daily treatment, when death occurred. These data demonstrate that measurement of circulating xenobiotics can be useful for the interpretation of genetic toxicology results. ©

ISSN:0893-6692    

DOI:10.1002/em.2850210110

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

年代:1993

数据来源: WILEY

摘要:

AbstractCytotoxic and cell transforming activities of the pesticides cyanazine, diflubenzuron, dithianon, procymidone, and vinclozolin were investigated in vitro by utilizing the BALB/c 3T3 cell transformation test performed in the presence or in the absence of S‐9 mix as an exogenous bioactivation system for the chemicals. All the assayed pesticides were cytotoxic in the absence of S‐9 mix, whereas only dithianon exerted cytotoxic effects in the presence of metabolic activation. All the chemicals tested did induce BALB/c 3T3 cell transformation, to a various extent, in the absence of S‐9 mix. Cell transforming ability of cyanazine and diflubenzuron was not detectable in the presence of S‐9. © 1993 Wiley

ISSN:0893-6692    

DOI:10.1002/em.2850210111

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

年代:1993

数据来源: WILEY