ISSN:0270-3211    

DOI:10.1002/tcm.1770040402

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

年代:1984

数据来源: WILEY

摘要:

AbstractSodium meclofenamate (Meclomen®), CI‐583, is an anthranilic acid salt developed as a nonsteroidal, antiinflammatory agent. A multitest battery of short‐term tests was employed to characterize the genotoxic and mutagenic potential of the compound by measuring point mutations in bacteria, induction of sister‐chromatid exchange, chromosome aberrations, and gene mutations in mammalian cells in vitro. In vitro assays included metabolic activation. The in vivo assay was for chromosome aberrations in bone marrow cells from rats. At toxicity‐limited doses for each assay, no activity was detected in the bacterial or mammalian cell mutation assays, and sister‐chromatid exchange frequencies were not increased over control rates. When sodium meclofenamate was evaluated in vitro, chromosome aberrations were induced under metabolic activation in CHO cells. Chromosome aberrations and clastogenic activity were not demonstrated after oral administration of Meclomen® to male rats. It was concluded that sodium meclofenamate does not possess overt mutagenic potential under these conditions. The activity seen in vitro with CHO cells after metabolic activation did not correlate with the results from the other tests and was attributed to the formation of reactive metabolites not present or formed in in v

ISSN:0270-3211    

DOI:10.1002/tcm.1770040403

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

年代:1984

数据来源: WILEY

摘要:

AbstractTo evaluate the toxicological effects of chemicals on preimplantation mammalian embryos, pregnant rats were treated with chlorambucil (0, 3, 6, and 12 mg/kg IP) on day 1, 2, or 3 of gestation (positive vaginal smear = day 0). Blastocysts were collected on day 4 and evaluated for gross morphology, cell number, and mitotic index. Some females treated on day 3 post coitum were sacrificed on day 20 and fetuses were evaluated for teratogenic effects. On day 4 of gestation a dose‐related reduction of cell number/embryo was recorded; this effect was most manifest with treatment on day 3 post coitum. The mitotic index was significantly higher in all treated groups. A dose‐related increase in “micronucleus‐like bodies” has been observed in treated embryos. A comparison with the micronucleus test in the bone marrow revealed a major sensitivity of the embryonic material. No malformations have been observed in fetuses at term, but their weights were significantly reduced and a dose‐related increase of postimplantation loss was recorded in trea

ISSN:0270-3211    

DOI:10.1002/tcm.1770040404

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

年代:1984

数据来源: WILEY

摘要:

AbstractHigh‐density cultures of mouse embryo limb bud cells differentiate and synthesize an extracellular matrix containing sulfated proteoglycans. Since these in vitro events are related to those that occur during fetal development, we have investigated the use of cultured limb bud cells for the analysis of the activities of chemical teratogens. We have established the conditions for the use of the radiochemicals35SO 4=and3H‐thymidine for the assessment of chemical effects on sulfated proteoglycan and DNA synthesis, respectively, in mouse limb bud cells. By performing double‐labeling experiments in the presence of test chemicals, the preferential inhibition of either proteoglycan synthesis or DNA synthesis could be demonstrated for 19 of 22 known mouse teratogens tested. The five nonteratogens tested did not cause significant differences in the inhibition of either macromolecular class. The overall predictive accuracy of the system was ∼89%, and the false‐negative rate was ∼14.8%. No false positives were observed. These data showed that this cell culture system differentiated between the activites of a limited set of selected mouse teratogens and nonteratogens, suggesting that cultured mouse embryo limb bud cells may constitute the basis for the development of a powerful tool for analyses of chemical teratoge

ISSN:0270-3211    

DOI:10.1002/tcm.1770040405

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

年代:1984

数据来源: WILEY

摘要:

AbstractThe cis and trans isomers of 1,2‐dichloroethylene were tested for mutagenic effects in a diploid strain (D7) of the yeast Saccharomyces cerevisiae in suspension tests with and without a mammalian microsomal activation system, an S9 mouse liver fraction, and by an in vivo intrasanguineous host mediated assay. The effects of the same agents on aminopyrine N‐demethylase activity and cytochrome P‐450 level in liver were studied in nonpretreated and in phenobarbital + β‐naphtoflavone‐pretreated mice. In the suspension test, both isomers exhibited dose dependent toxicity, and survival was lower with metabolic activation than without. In this test also, both isomers exhibited genetic activity as measured by increases in recombinants at theade2 locus in experiments with metabolic activation. In the host‐mediated assay, only the cis isomer showed evidence of mutagenic activity with significant increases in convertants at thetrplocus and revertants at the ilv locus. Such mutagenic activity was found both after acute and chronic doses and in liver, kidney, and lung tissue. The two isomers exhibited different effects with respect to aminopyrine N‐demethylase activity and cytochrome P‐450 level. In general, the trans isomer appeared to emphasize induction of enzyme activity or level while the cis isomer more frequently tended to inhibit activity or de

ISSN:0270-3211    

DOI:10.1002/tcm.1770040406

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

年代:1984

数据来源: WILEY

摘要:

AbstractTwo closely related retinoids, all‐trans and 13‐cis retinoic acids, were assessed for their relative activities as teratogens in ICR mice by monitoring the frequency with which either isomer produced discrete dysmorphogenesis of the embryonic limb and the secondary palate. A single oral dose of all‐trans retinoic acid at 100 mg/kg on either day 11.5 or 12.0 of gestation (plug day = day one) was maximally effective; more than 90% of the treated embryos developed reduction defects of the limb bones and an equally high percentage also had cleft palate. The limb development was most sensitive on day 11.5 of gestation while the peak susceptibility for palatal clefts began on day 12.0. Under identical experimental conditions, treatment with 100 mg/kg 13‐cis retinoic acid produced no apparent teratogenic effects. By assessing the relative incidence of readily identifiable malformations of the limb and palate associated with various doses of the two isomers, we found that 13‐cis retinoic acid was four to eight times less embry‐opathic than all‐trans retinoic acid. Since the mechanism of teratogenic action of retinoids is still far from clear, it is suggested that further studies on causative factors will be greatly assisted by the use of these two closely related retinoids, which substantially differ from each other in their terato

ISSN:0270-3211    

DOI:10.1002/tcm.1770040407

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

年代:1984

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770040408

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

年代:1984

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770040401

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

年代:1984

数据来源: WILEY