摘要:

AbstractThe BALB/3T3 clone A31‐1‐1 mouse embryo cell line at passages 7 to 13 was selected for morphologic studies of neoplastic transformation by carcinogens of different chemical classes, in the absence of any added extracellular metabolic activation. Dose‐related transforming activity was demonstrated for the carcinogens aflatoxin B1(AFB) and benzidine (BZ) not previously reported in this system, and was confirmed for benzo[a]pyrene (BP), 3‐methylcholanthrene (MCA), andN‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG). Spontaneous transformation per cells at risk was low (0.14 type III foci x 10−4), while chemically induced transformation was 2 to 3 orders of magnitude higher with all compounds. The molar concentration of carcinogens in complete medium, required to induce a transformation frequency of 1.0 type III foci x 10−3showed the highest level of activity for BP (0.04 μm), an intermediate level for AFB (0.2 to 1.4 μm), MCA (1.1 μm), and MNNG (2.3 μm), and the lowest level of activity for BZ (30.0 μm). The dose‐related induction of morphological transformation in this clone by carcinogens of different classes indicates the potential value of this biological system in quantitative studies of carcinogen combinations,

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:2<101::AID-TCM1770030202>3.0.CO;2-L

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

年代:1983

数据来源: WILEY

摘要:

AbstractTheVeratrum‐derived steroidal alkaloid, jervine, induces cyclopia and limb malformations in sheep, and various other craniofacial malformations in several other mammalian and avian species. In the present study, the question whether jervine acts directly or indirectly on mammalian embryos to produce malformations and the nature of the target tissue or cells were examined using whole‐embryo cultures of the CD rat. Embryos were explanted into culture at the presomite, early neurula stage and cultured in the presence or absence of jervine for 48 hours. Jervine (at 1–5 μg/ml) induced an oblong‐head appearance and ventrally displaced optic vesicles, with little or no other effects observed on overall growth and development. The specific target tissue in the embryo was found to be the cranial neuroepithelium. This specificity of action is quite unusual since most teratogens examined in whole‐embryo culture to date have various nonspecific effects on embryonic growth and diffe

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:2<111::AID-TCM1770030203>3.0.CO;2-F

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

年代:1983

数据来源: WILEY

摘要:

AbstractAfter N‐methyl‐N′‐nitro‐N‐nitrosoguanidine(MNNG) treatment of density‐inhibited postconfluent (DDIR) Syrian hamster embryo cell cultures, only a small population of the cells incorporate [3H]‐thymidine within the next 10–20 h. The transformed colonies, observed subsequent to reseeding, are derived from the population incorporating [3H]‐thymidine. This study demonstrates that MNNG‐induced thymidine incorporation resulted from semiconservative DNA synthesis as analyzed by DNA density gradients. Furthermore, cell cycle distributions at selected times after treatment indicate that the MNNG‐responsive population was released from the density‐dependent G1 block, proceeded through S, and became blocked again at G2 or M. These results indicate that DNA synthesis is temporally related to an ear

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:2<123::AID-TCM1770030204>3.0.CO;2-7

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

年代:1983

数据来源: WILEY

摘要:

AbstractAcetazolamide, an inhibitor of the enzyme carbonic anhydrase (E.C. 4.2.1.1.), causes a unique congenital anomaly characterized by postaxial reduction of the distal portion of the right forelimb. To gain an understanding of the mechanism of teratogenesis, the activity of carbonic anhydrase in sensitive and resistant mouse strains, and its inhibition by acetazolamide, were examined. Differences in teratologic sensitivity were found not to be attributable to differences in maternal or embryonic drug levels. Enzyme inhibition at acetazolamide concentrations ranging between 10−11and 10−5M did not differ between the mouse strains when adult erythrocytes or day 12 embryos were assayed. However, in day 10 embryos, the period of maximum teratologic susceptibility, a small strain difference was found which suggested that the form of carbonic anhydrase in the susceptible CBA/J strain at this time is somewhat more sensitive to inhibition by acetazolamide than the form found in the resistant SWV strain. The results suggest further that more than one isozyme of carbonic anhydrase may be present in all three samp

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:2<133::AID-TCM1770030205>3.0.CO;2-1

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

年代:1983

数据来源: WILEY

摘要:

AbstractGram‐negative urinary tract infections in pregnant women have been implicated as causes of maternal endotoxemia and a subseqent higher incidence of malformations in their offspring. A study was performed to evaluate the effects of endotoxin on the development of the golden hamster. Endotoxin was shown to be extremely embryolethal at higher doses and to produce several malformations at lower doses. The pregnant hamster and its developing embryos were observed to be far more sensitive to endotoxin than species examined by other investigator

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:2<145::AID-TCM1770030206>3.0.CO;2-U

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

年代:1983

数据来源: WILEY

摘要:

AbstractThe isolated perfused rabbbit lung (IPL) is being used to study the effects of particulate exposure on the pulmonary metabolism of benzo(a)pyrene (BaP). Pasturealla‐free New Zealand white rabbits were treated intraperitoneally with BaP prior to kill. The isolated lungs were then administered either14C‐labeled BaP alone or BaP plus Fe2O3or fly ash by intratracheal injection. Rates of appearance of BaP metabolites in the perfusing blood were determined. The extent of metabolism, distribution of metabolites, and types of metabolites produced were quantified for various lung tissue types by high‐performance liquid chromatography and liquid scintillation spectrometry. Procedures were developed to apply theSalmonella/microsome test in the assay of mutagenicity of lung tissue and blood extracts as an indicator of their biologic activity. With few exceptions, blood extracts from IPL receiving BaP only were not mutagenic. Lung, trachea‐bronchi, and macrophage extracts, by contrast, were mutagenic. A part of this activity could be attributed to BaP metabolites rather than to parent compound remaining in extracts. When lungs were exposed to Fe2O3or to fly ash, only macrophage extracts were consistently mutagenic. This activity was due to significant amounts of unmetaboli

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:2<151::AID-TCM1770030207>3.0.CO;2-S

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

年代:1983

数据来源: WILEY

摘要:

AbstractSeven dithiocarbamates and three acetates were tested for teratogenicity and lethality in three‐day chicken embryos. These included: cadmium diethyldithiocarbamate (CdDE), zinc diethyldithiocarbamate (ZnDE), zinc ethylphenyldithiocarbamate (ZnEP), zinc dibutyldithiocarbamate (ZnDB), copper dimethyldithiocarbamate (CuDM), tellurium diethyldithiocarbamate (TeDE), and piperidine pentamethylenedithiocarbamate (PPM), cadmium acetate (CdAC), copper (II)acetate (CuAC), and zinc acetate (ZnAC). The parameters measured were early deaths, recorded within two days of injection, late deaths of malformed embryos, late deaths of nonmalformed embryos, and malformed survivors. The order of embryotoxicity decreased as follows: CdAC>CdDE>ZnDE ≥ ZnEP ≥ ZnDB>CuDM>TeDE>CuAC>PPM>ZnAC. The only exception to this order was the relatively weak teratogenicity of the metal acetates as compared to dithiocarbamates. Cadmium and zinc dithiocarbamates were potent embryotoxic agents eliciting lethality and malformations at doses of 1 to 10 nmole per egg. Most embryonic deaths occurred at stages 29 to 31, and most of the dead embryos were malf

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:2<163::AID-TCM1770030208>3.0.CO;2-K

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

年代:1983

数据来源: WILEY

摘要:

AbstractThe answers to a questionnaire sent to 147 laboratories in Europe using theSalmonella/mammalian‐microsome assay are presented. In mutagenicity testing, where research projects in environmental mutagenesis predominate, theSalmonella/mammalian‐microsome assay is the most often used test. Of all laboratories that answered the questionnaire, 80% are using the test with occasional modifications (preincubation, fluctuation test). Most of the differences concern the activation system used. This questionnaire is part of a European collaborative study which aims to improve the standardization of theSalmonella/mammalian‐microsome

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:2<177::AID-TCM1770030209>3.0.CO;2-A

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

年代:1983

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:2<183::AID-TCM1770030210>3.0.CO;2-0

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

年代:1983

数据来源: WILEY

摘要:

AbstractThe influence of various parameters and growth conditions in the “overnight culture” ofSalmonella typhimuriumstrains on mutagenicity test results was investigated. A number of factors were first suspected to be of some importance for the quantitative outcome of the mutagenicity test. None of them, however, was found to influence the results to such a marked extent as to be a major source of variability. Only the brand of nutrient broth used for the propagation of the bacteria proved finally to have a certain effect on the number of (spontaneous and induced) revertant colonies, although no precise and quantitative statements can be made with regard to a possible standardization of this experimental segment in theSalmonellamutagenicity test. The occurrence of such unpredictable but noticeable influences is, however, evidence for the importance of an intralaboratory optimization and standardization of all parts of the test proced

ISSN:0270-3211    

DOI:10.1002/1520-6866(1990)3:2<187::AID-TCM1770030211>3.0.CO;2-U

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

年代:1983

数据来源: WILEY