摘要:

AbstractThree animal species used in in vivo mutagenicity testing—rats, mice and Chinese hamsters—were compared with respect to their mutagenic response to the mycotoxin aflatoxin B1 (AFB1). The micronucleus test and the SCE test with bone marrow cells were chosen as test methods, employing similar protocols for all species. The mutagenic potential of AFB1 was detected with rats and mice but not with Chinese hamsters. Rats were more susceptible to the mutagenic action of AFB1 than mice with regard to the effective dose. A difference in sensitivity between males and females was evident in rats and mice: male animals exhibited higher induced micronucleus frequencies than females, and a clear SCE‐inducing effect was only detectable in male animals. These results are in agreement with those of in vitro and carcinogenicity studies. They may be due to metabolic differences between the species and sexes, predominantly differences in glutathion conjugation of the reactive AFB1 epoxide and in the formation of the metabolite aflatoxicol. Furthermore, it could be demonstrated that AFB1 seems to be a more potent inducer of micronuclei than of SCE. Since our results obtained with rats and mice were clearly positive, but with the Chinese hamster the mutagenic potential of AFB1 was not detectable with the test systems used, it can be concluded that the choice of an “inappropriate” test species may lead to a false negative judgment on the genotoxic potential of a test

ISSN:0270-3211    

DOI:10.1002/tcm.1770060102

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

年代:1986

数据来源: WILEY

摘要:

AbstractTo test the recently developed method of exposing cells to volatile compounds, phytohemagglutinin‐stimulated human peripheral lymphocyte cultures were exposed to gaseous methyl bromide, ethylene oxide, and proplyene oxide, as well as diesel exhaust. The cultures were placed in sterile dialysis tubing and inserted into enclosed flasks containing additional culture medium. The test compounds (in gaseous state) were diluted with air and bubbled through the flasks for various lengths of time. The cells were then washed and incubated for a total of 75 h. The harvest was performed according to established procedures, and second‐division cells were scored for induction of sister chromatid exchanges (SCEs). The SCE frequency was more than doubled in the cultures treated with ethylene oxide and propylene oxide; methyl bromide also induced SCEs. Cultures treated with diesel exhaust showed an increase in the SCE frequency in cells from two of four donors tested. These results further substantiate the use of this method for detecting the induction of SCEs by airborne genotox

ISSN:0270-3211    

DOI:10.1002/tcm.1770060103

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe fluorescein diacetate test is a measure of both esterase enzyme activity and membrane integrity and it has been shown to be useful in assessing the viability of a variety of cells cultured in vitro, mouse embryos after freezing and thawing, and mouse embryos grown under inadequate culture conditions. In this study, the effects were examined of cyclophosphamide and sodium valproate administered respectively to pregnant inbred CBA mice 60 h after fertilization, on the viability of 84‐h blastocysts. Cyclophosphamide 20 and 40 mg/kg bodyweight and sodium valproate 90 mg/kg significantly increased the number of nonviable blastocysts. Cyclophosphamide 4 mg/kg and sodium valproate 23 and 45 mg/kg did not adversely affect blastocyst viability. The intensity of embryo fluorescence correlated well with the subsequent development of the embryos in culture (r = 0.863; p<0.001). The test had a sensitivity of 83% and a specificity of 100%. Exposure of embryos to fluorescein diacetate under the conditions of this experiment did not adversely influence the subsequent postimplantation development of 84‐h blastocysts cultured in vitro for a further 120 h. These findings suggest that the fluorescein diacetate test is a simple, rapid, and nontoxic procedure that may be useful in assessing the viability of preimplantation embryos after exposure to embryotoxic drugs and chemic

ISSN:0270-3211    

DOI:10.1002/tcm.1770060104

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe present study is an evaluation of the developmental toxicity of dinocap in three rodent species using an in vivo teratology screen. Our protocol uses postnatal viability, weight gain, and morphological and behavioral development through weaning to assess the developmental toxicity of compounds.Dinocap administered orally on days 7 to 16 of gestation to the CD‐1 mouse resulted in increased postnatal mortality at 25 mg/kg/d (80% in block 1 and 40% in block 2). Many of the treated pups that died during the neonatal period were “ballooned” and had cleft palates. Although there was no treatment related mortality in the 12 mg/kg/d dosage group, 6% (14/226) of these mice and 24% (23/96) of the survivors from the 25 mg/kg/d dosage group displayed torticollis (a twisting of the neck resulting in an abnormal tilting of the head). These tilted‐head mice held the head and forepart of the body tilted constantly to one side, both when resting and walking. The tilt was in either direction but was always constant for a given animal; in different mice, the angle varied considerably from almost 0 to 30°. Some mice circled repeatedly in one direction in the home cage, others bobbed their heads and did back‐flips, while others rolled over, always rolling in the same direction.In the hamster, developmental toxicity was seen at (100 and 200 mg/kg/d) or near (50 mg/kg/d) maternally toxic doses but no behavioral alterations were noted and none of the pups were ballooned.The highest dose of dinocap (100 mglkgld during days 7–20) used in the rat study produced mild maternal toxicity (reduced maternal weight gain from day 3 to 10 of gestation), but did not alter the postnatal development of

ISSN:0270-3211    

DOI:10.1002/tcm.1770060105

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

年代:1986

数据来源: WILEY

摘要:

AbstractThe effects of maternal protein‐energy malnutrition and exposure to nitrofen on selected aspects of intestinal morphology and function were studied in the fetal rat. Pregnant rats were fed, throughout gestation, diets containing 24% or 6% casein as the sole source of protein. Reduced total food intake produced protein‐energy malnutrition (PEM). Each diet group was divided in half and gavaged with either 12.5 mg nitrofen in corn oil/kg/day or corn oil carrier only from days 7 to 21 of gestation. Body weight, intestinal weight, length, and diameter were measured as were villus length (VL), villus width (VW), and number of villi per length of intestine (VMM). Protein (horseradish peroxidase) and lipid absorption were studied histochemically. Lactase and dipeptidase activities were determined in proximal, medial, and distal thirds of the intestine. Results showed that the restricted maternal diet resulted in reduced fetal body weight (BW), intestinal weight (IW) and length (IL), reduced IW/BW and IW/IL ratios, VH, and VMM. The VW was reduced only in the distal third. Protein and lipid absorption were unaffected. Lactase and dipeptidase activities were reduced. Maternal nitrofen exposure resulted in reduced body weight, intestinal size, and lipid absorption, with some evidence of interaction with the diet effects on enzyme activities. It is concluded that effects of maternal malnutrition were extensive, but that nitrofen exposure, at this dosage level, is not likely to contribute to the postnatal fetal mortality rate in either adequately nourished or malnourished r

ISSN:0270-3211    

DOI:10.1002/tcm.1770060106

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

年代:1986

数据来源: WILEY

摘要:

AbstractRetention of3H‐moxestrol in mouse fetuses after transmaternal, intrafetal, and intraplacental injection were compared. Direct injection into the allantoic placenta resulted in greater retention of radioactivity by the fetus than the other modes of administration between 12 and 16 days of gestation. By this same criterion, intrafetal injection was best for older fetuses. Maternal injection was the least efficient way to transfer3H‐moxestrol to the fe

ISSN:0270-3211    

DOI:10.1002/tcm.1770060107

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

年代:1986

数据来源: WILEY

摘要:

AbstractSix monofunctional alkylating agents, trenimon, cyclophosphamide, and isoniazid were proven for transplacental cytogenetic activity in mouse embryos at day 10 of gestational age under the same conditions as used in the mammalian spot test. With the exception of isoniazid, all compounds led to an increase in the aberration frequencies in embryonal cells. The results were statistically not significant in the case of EMS, while all other chemicals showed a dose‐dependent clastogenic activity. After treatment with monofunctional alkylants, chromatid breaks were dominating, while polyfunctional compounds also produced chromatid exchanges, especially in the case of trenimon. ENU and DMS showed a very early aberration maximum 6 hr after injection. For both compounds, very similar dose‐response curves were found for induction of chromatid breaks in the dose range 10‐75 mg/kg. There is no correlation between the Swain‐Scott factors of monofunctional alkylants and their ability to induce chromosomal damage when compared in terms of pharmacological doses.A quantitative comparison of data found in the cytogenetic test in embryonal cells with those obtained in the mammalian spot test led to the conclusion that chromosomal mutations are of minor relevancy for the expression of recessive alleles in heterozygous mouse embryos. With this respect, the mammalian spot test must be considered as an in vivo test for the detection of gene mutations in somatic cells of th

ISSN:0270-3211    

DOI:10.1002/tcm.1770060108

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

年代:1986

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770060109

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

年代:1986

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770060101

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

年代:1986

数据来源: WILEY