摘要:

AbstractHigh densities of 6‐thioguanine‐sensitive Chinese hamster V79 cells reduce the recovery of co‐cultured 6‐thioguanine‐resistant cells through a form of intercellular communication (metabolic cooperation). Diphenylhydantoin and phenobarbital, suspected human and animal teratogens and tumor promoters, were able to inhibit intercellular communication at noncytotoxic doses. A potentiation was observed when a mixture of the two chemicals

ISSN:0270-3211    

DOI:10.1002/tcm.1770050602

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

年代:1985

数据来源: WILEY

摘要:

Abstract1,2‐Dibromoethane (DBE) and two of its potential metabolites, bromoethanol (BE) and bromoacetaldehyde (BA), were tested for carcinogenicity in male and female B6C3F1 mice using 30 animals of each sex per group. The carcinogen DBE was included in this assay as a positive control. The compounds were administered in distilled drinking water using equimolar concentrations, 4 mmol, of the chemicals. The dose chosen was based on subchronic bioassays of three months' duration. The chronic tests were continued for ∼450 days in the case of DBE and ∼560 days for both BE and BA. DBE induced squamous carcinomas of the forestomach in 22 females and 26 males and squamous papillomas of the esophagus in 3 females. BE induced squamous papillomas of the forestomach only in 10 females and 9 males. BA did not induce a significant incidence of tumors of the forestomach. Significant tumor incidences at other sites were not observed in any groups including the distilled water control group. Based on these findings, it is unlikely that BE or BA are activated carcinogenic intermediates o

ISSN:0270-3211    

DOI:10.1002/tcm.1770050603

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

年代:1985

数据来源: WILEY

摘要:

AbstractThe carcinogens N‐2‐acetylaminofluorene (AAF) and diethylnitrosamine (DEN) often give negative results when tested in the Fischer rat embryo cell survival assay with the standard single 72‐hour regimen, whereas another carcinogen, benzo(a)pyrene [B(a)P], may yield varied results between different laboratories and may require relatively high concentrations (compared with other polycyclic aromatic hydrocarbons) for a positive result to occur. Enhanced survivals (compared with controls) were 56% or less with these carcinogens. In place of the standard single 72‐hour treatment with test chemical, the cells were exposed to three consecutive 24‐hour treatments. The amount of B(a)P metabolized during the last of the three 24‐hour treatment periods was 3.2 times greater than that during the first 24‐hour period, indicating that an induction effect occurred. Furthermore, the total amount of metabolites of B(a)P formed with repetitive treatments was 2.1 times greater than with a single 72‐hour treatment. The total amount of AAF metabolites formed with repeated treatments was 1.6 times greater than with the single treatment regimen, although no induction effect was observed between treatment periods. Survival enhancement with the repetitive regimen increased to 181% with B(a)P, 172% with AAF, and 188% with DEN. With benzo(e)pyrene, anthracene, and pyrene, enhanced survival was 14% or less following the single treatment regimen and did not increase following repetitive treatments. When the carcinogen cinnamyl anthranilate was tested using repetitive treatments, survival enhancement was more than 100% at three of six doses, versus less than 0% when the standard single treatment r

ISSN:0270-3211    

DOI:10.1002/tcm.1770050604

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

年代:1985

数据来源: WILEY

摘要:

AbstractArotinoid ethyl ester (RO 13‐6298) is a new and very potent retinoid that exerts a profound influence on epithelial and mesenchymal differentiation in doses 500 times lower than those of compounds of the first and second retinoid generation. In the present study the teratogenicity of arotinoid ethyl ester was investigated in NMRI mice employing different treatment schedules. Recording of abnormalities was performed on day 18 (day 0 = day of conception) according to Wilson and with cleared skeletal preparations.Intraperitoneal application of the drug at a dosage of 10 μg/kg/day for three consecutive days (days 9–11 or 12–14) caused severe malformations, particularly in the skeletal system and the cavernous organs. Skeletal elements were reduced in number, shortened, or abnormally shaped. Ossification was diminished. Atresiae of anus and urethra were frequent. Single application of 200 μg/kg between days 8 and 14 also caused multiple and severe malformations. However, no stagespecific pattern of abnormalities was detectable. Some skeletal malformations indicated more or less vulnerable stages that were in concordance with special developmental steps. Others, however, seemed to be equally susceptible over a longer period, eg, rays 1 and 5 of the hand or foot and the development of the mandibular joints. The pattern of abnormalities caused by these very low doses of RO 13‐6298 is comparable to that obtained with other retinoids and is achieved within the same relative dose‐response range. Preconceptional treatment of the animals did not induce any ma

ISSN:0270-3211    

DOI:10.1002/tcm.1770050605

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

年代:1985

数据来源: WILEY

摘要:

AbstractThe influence of ethanol consumption on cleft palate induction by methylmercury, cortisone, and retinyl acetate was investigated in Swiss white mice. Consumption of 20% ethanol throughout gestation significantly increased the incidence of cleft palate compared to water‐fed mice, when methylmercury was given on four consecutive days (days 9–12, 5 mg/kg of body weight). Ethanol also increased the incidence of cleft palate in mice given retinyl acetate (3,400 or 5,100 IU) on day 12, compared to retinol acetate‐treated mice given water, but did not affect cleft palate induction by cortisone (2.5 mg/d, days 8–11). Ethanol significantly reduced fetal weight in the presence or absence of the three teratogens, but the results do not support a hypothesis that growth retardation is directly responsible for the potentiating action of ethanol. It may be that ethanol acts to increase cleft palate induction by some teratogens by retarding fetal developmental pr

ISSN:0270-3211    

DOI:10.1002/tcm.1770050606

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

年代:1985

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770050607

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

年代:1985

数据来源: WILEY

摘要:

AbstractMicrovillous membrane vesicle preparations from the maternal surface of human placental syncytiotrophoblast were examined for the presence of carnitine and choline acetyltransferase activity. Radiometric assay for acetylcholine employed butyronitrile‐tetraphenylboron extraction of the quaternary ions. Acetylcarnitine was assayed by anion exchange chromatography. The data reveal that carnitine is the primary substrate for the vesicle acetyltransferase enzyme(s), whereas choline appears to be a minor substrate. For acetylcarnitine synthesis, the Kmis 0.749 mM carnitine and Vmaxis 641 pmol·mg protein−1·minute−1, respectively; for acetylcholine synthesis, the Kmis 0.5 mM choline and Vmaxis 53 pmol·mg protein−1·minute−1, respectively. Approximately ten times more acetylated product was formed with carnitine than with choline. The carnitine‐mediated reaction obeyed Michaelis‐Menten kinetics, whereas the choline reaction exhibited anomalous behavior. Vesicle preparations were stable for 21 days at —80°C. Preliminary studies on hypotonically lysed vesicles demonstrate that the acetyltransferase is particulate and is bound to the membrane of the vesicle. These findings demonstrate that carnitine acetyltransferase activity is in the plasmalemma membrane of the syncytiotrophoblast and suggest a role for this enzyme, analogous to the mitochondrial fatty acid shuttle system, in the maternofetal translocation of

ISSN:0270-3211    

DOI:10.1002/tcm.1770050608

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

年代:1985

数据来源: WILEY

摘要:

AbstractBilateral or unilateral intraovarian injection with the polycyclic aromatic hydrocarbons 3‐methylcholanthrene (3‐MC), or 7,12‐dimethylbenz(a)anthracene (DMBA) destroys oocytes in C57BL/6N and DBA/2N mice. The threshold for small oocyte destruction following bilateral intraovarian treatment with 3‐MC was between 0.1 and 1 μg/ovary in both DBA/2N and C57BL/6N mice. After intraovarian treatment with DMBA, a more potent ovotoxin, the thresholds for small oocyte destruction were between 0.01 and 0.1 μg/ovary. Calculated ED50's for small oocyte destruction following bilateral intraovarian treatment with 3‐MC were C57BL/6N, 0.33 μg/ovary; DBA/2N, 1.02 μg/ovary—for DMBA the ED50's were C57BL/6N, 0.11 μg/ovary; DBA/2N, 0.03 μg/ovary. Unilateral intraovarian treatment also destroyed oocytes in the treated ovary. Treatment with intraperitoneal alpha‐naphthoflavone (ANF), a competitive inhibitor of polycyclic aromatic hydrocarbon metabolism by microsomal monooxygenases, inhibited oocyte destruction. Intraovarian treatment with ANF decreased oocyte destruction produced by intraovarian DMBA. These data suggest that both 3‐MC and DMBA are indirect acting ovotoxins requiring metabolic activation before oocyte destruction occurs. In addition, these data also suggest that the ovary contains the enzymes necessary to biotransform xenobiotics like 3‐MC and DMBA to ovotoxic metabolites. Metabolic activation of xenobiotics to reactive productswithinthe ovary may represent a special threat to the

ISSN:0270-3211    

DOI:10.1002/tcm.1770050609

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

年代:1985

数据来源: WILEY

摘要:

AbstractStructural malformation of the oviduct has been reported in experimental animal models and women following prenatal exposure to diethylstilbestrol (DES). To study histological changes in the oviduct in the absence of gross structural malformation, neonatal CD‐1 mice were treated with DES (2 μg/pup/day) on days 1–5 of age. Focal epithelial hyperplasia was present at 1 month of age in 16 out of 18 (89%) of the DES‐treated mice. At 4 months of age, general epithelial hyperplasia with multiple gland‐like structures into and through the muscle wall of the oviduct was observed in 90% of the treated mice; by 12 months of age, epithelial hyperplasia and pseudogland formation were seen in 100% of the DES‐exposed animals. Epithelial hyperplasia and gland formation were not observed in control mice. The alteration induced by DES in the differentiation and proliferation of mouse oviductal epithelium suggests that the oviduct is a target for DES toxic effects. In addition, there was a progression of the epithelial changes with age. The histological changes described in this study may be partially responsible for the decreased fertility previously reported in this mouse model. Similar changes in the oviduct of DES‐exposed women remain to b

ISSN:0270-3211    

DOI:10.1002/tcm.1770050610

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

年代:1985

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770050601

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

年代:1985

数据来源: WILEY