摘要:

AbstractThe effects of methylnitrosourea (MNU) on the development of preimplantation mouse embryos were investigated in this study. ICR mice were treated intraperitoneally with single doses of 10, 20, and 30 mg MNU/kg body wt on day 0, 1, 2, or 3 of pregnancy. The uterine contents were examined on day 18 of pregnancy. The fetuses were examined for external and skeletal abnormalities. No significant differences were observed in the number of implantation sites between all the MNU‐treated groups and controls. MNU treatment on day 2 or 3 of pregnancy caused dose‐dependent significant increases in the incidence of abnormal fetuses over the control level, while treatment on day 0 or 1 failed to cause an increase of abnormalities. Cleft palate, exencephalus, and malformed vertebrae were the most common types of abnormalities. In the embryo transfer experiments, the frequency of fetal abnormalities induced when embryos were transferred from MNU‐treated females to untreated pseudopregnant females was significantly higher than that induced when embryos were transferred from untreated females to MNU‐treated or untreated pseudopregnant females. The results in the present study confirm and extend the previously proposed hypothesis that the direct effects of MNU on preimplantation embryos make a significant contribution to the induction of fetal malfor

ISSN:0270-3211    

DOI:10.1002/tcm.1770110102

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe variant frequencies for 6‐thioguanine‐resistant spleen cells in different mouse strains have been estimated by autoradiography for animals without chemical treatment and in cases of in vivo mutagen dosage with ethylnitrosourea and cyclophosphamide, respectively. In untreated mice, the following variant frequencies have been found: C57B1/6J, 2.84 × 10−5;NMRI, 3.04 × 10−5;DBA/2J, 5.91 × 10−5. The selective concentration of 6‐thioguanine was 100 μM for strains NMRI and DBA, while in the case of C57B1 with this concentration, no variant cells could be counted and a selective concentration of 50 μM was chosen. Treatment with 70, 140, and 210 mg/kg ethylnitrosourea resulted in increased variant frequencies in cells isolated 8 or 15 days later. On the other hand, doses of 20, 60, and 120 mg/kg cyclophosphamide did not result in a clear dose‐response relationship of variant frequency in cells isolated 1, 8, 15, 22, and 29 days after treatment. These data are discussed with respect to findings in human populations exposed occupationally t

ISSN:0270-3211    

DOI:10.1002/tcm.1770110103

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

年代:1991

数据来源: WILEY

摘要:

AbstractIt has been reported that fractionated doses of 13‐cis‐retinoic acid are disproportionately more embryotoxic in pregnant mice than is the same dose given in a single bolus. Here, we examined limited pharmacokinetic profiles of a single (100 mg/kg dose given to NMRI mice on day 11 of gestation) versus multiple (3 × 100 mg/kg, 4 h apart) doses in an effort to assess the relative contribution to teratogenicity made by the drug and/or its metabolites. The major plasma metabolite of 13‐cis‐retinoic acid in the mouse was 13‐cis‐retinoyl‐β‐glucuronide, followed by the 4‐oxo metabolites and all‐trans‐retinoic acid. Transfer to the mouse embryo was very efficient for all‐trans‐retinoic acid, whereas, it was tenfold less efficient for 13‐cis‐retinoic acid and 100‐fold less efficient for 13‐cis‐retinoyl‐β‐glucuronide. The isomer all‐trans‐retinoic acid was found in the placenta at concentrations two‐ to three‐fold higher than in the plasma, suggesting placental accumulation as well as placentalcis/transisomerization. Since 13‐cis‐retinoyl‐β‐glucuronide and 13‐cis‐ and all‐trans‐retinoic acid were detected in the embryo after this multiple dosing schedule, any of the three or their combinations may have been involved in the induction of malformations, but all‐trans‐retinoic acid, a well‐known potent teratogen detected at concentrations of between 590 and 80 ng/g fo

ISSN:0270-3211    

DOI:10.1002/tcm.1770110104

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe usefulness of an in vitro assay for embryotoxicity may depend on the availability of metabolic activation systems that will function in the culture system. The fetal mouse salivary gland has been investigated as an in vitro assay system. To see if the glands would grow in the presence of metabolic activators and if the glands would react to metabolites known to be embryotoxic, the glands were grown in the presence of cyclophosphamide (CP) and several activation systems. These included isolated rat hepatocytes, uninduced rat S‐9, rat S‐9 induced with 3‐methylcholanthrene (3‐MC), rat S‐9 induced with Aroclor 1254, and human S‐9. Twenty salivary glands were isolated from 13 day embryos (plug day = 0) and were grown in each treatment for 48 h. One control had no activation system or CP, one had an activation system but no CP, and three treatments had the activation system and 25, 75, or 150 μg/ml CP. The S‐9 with cofactors and the appropriate amount of CP was contained in dialysis bags. The greatest suppression of salivary gland growth occurred in co‐culture with hepatocytes activating CP. The S‐9 induced by Aroclor 1254 was nearly as effective as the hepatocytes. The next most effective was a group with similar activity consisting of the uninduced rat S‐9 and the three samples of human S‐9. The 3‐MC‐induced S‐9 was the least effective in suppressing growth of salivary glands. All the activation systems tested can be used with the s

ISSN:0270-3211    

DOI:10.1002/tcm.1770110105

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe rules of molecular geometry for predicting carcinogenic activity of polynuclear aromatic hydrocarbons (PAH) have been applied to a series of 50 unsubstituted PAH, and predicted carcinogenic activity is in good agreement with the results of testing for complete carcinogenic activity in mice and/or rats. The rules were developed from a knowledge of the center or centers of highest chemical or biochemical reactivity and are consistent with a unified hypothesis which states that the first step in the metabolic activation of unsubstituted PAH is the biochemical introduction of a methyl group. This bioalkylation reaction 1) takes place between certain PAH andS‐adenosyl‐L‐methionine and is catalyzed by cytosolic methyltransferase, 2) offers a means of probing for centers of reactivity in PAH, 3) provides a biochemical link between unsubstituted preprocarcinogens of aromatic type ArX and alkyl‐substituted procarcinogens of aromatic type ArCH2X (where X = H), and 4) makes it possible to include compounds of both aromatic types, in a consistent theory of aromatic hydrocarbon activation which incorporates alkyl substitution. The present study reveals that there are structural determinants of carcinog

ISSN:0270-3211    

DOI:10.1002/tcm.1770110106

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe potential mutagenic activity of hexachlorobenzene (HCB) and pentachloroanisole (PCA) was investigated. No genotoxicity after application onSalmonella typhimurium(Ames test),Escherichia coli, and human peripheral blood lymphocytes in vitro was observed.

ISSN:0270-3211    

DOI:10.1002/tcm.1770110107

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

年代:1991

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770110108

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

年代:1991

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770110101

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

年代:1991

数据来源: WILEY