摘要:

AbstractLinear alkanes of specific chain length were found to enhance differentially the mitogenic response of murine spleen lymphocytes to the lectin phytohemagglutinin. Within the homologous series of compounds having between six and eighteen carbon atoms, a biphasic structure–function relationship was found, with maximum comitogenic activity occurring for tetradecane, and none or little for octane and octadecane. No alkane was mitogenic per se, and no alkane displaced the optimum mitogenic concentration of the lectin. The concentration of tetradecane having equivalent comitogenic activity was similar to that of methyl myristate, a simple alkyl ester of equal alkyl chain length, but approximately four orders of magnitude less that of the potent promoter 12‐0‐tetradecanoylphorbol‐13‐acetate (TPA). A similar ratio of potencies of TPA and the alkane dodecane, also a lymphocyte comitogen, has previously been found for promotion of mouse epidermal tumorigenesis. Maximum comitogenic activity was found when alkane and lectin were added to cultures simultaneously, the effect decreasing sharply when alkane addition was delayed relative to lectin. These findings suggest the existence of a cellular receptor with specificity for hydrophobic functions with chain lengths lying within a restricted range. Binding to this receptor also appears to be a common early event in tumor promotion, comitogenicity, and comutagenicity by agents of several chemi

ISSN:0270-3211    

DOI:10.1002/tcm.1770010402

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

年代:1981

数据来源: WILEY

摘要:

AbstractWhile the dominant lethal (DL) assay is often used to assess the mutagenic potential of suspect agents, questions remain concerning its sensitivity, the appropriate way to analyze resultant data, and the necessary study size. Many questions surrounding the statistical analysis methods relate to a specification of the basic independent unit of experimentation and analysis, the particular type of study design used, and the distributional properties of the study variables. These statistical analysis issues must be resolved before adequate attention can be given to the related questions of experimental sensitivity and sample size. This report deals with the development of a statistical analysis methodology which incorporates a particular type of data clustering scheme to achieve desirable distributional properties of the measured variables so that analysis of variance (AOV) and related parametric testing procedures can be used. Further, the differences between dose groups which can be detected using 20, 10, and 5 cluster units of 6 males and 18 females each are estimated for each variable according to the size of selected Type I and II errors. While these procedures were developed in part using data from two replicate studies on the DL effects of differing doses of n‐butyl glycidyl ether in mice, the clustering scheme suggested can be used with other AOV and regression procedures corresponding to the specific study design employe

ISSN:0270-3211    

DOI:10.1002/tcm.1770010403

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

年代:1981

数据来源: WILEY

摘要:

AbstractDaily injections of epidermal growth factor (EGF) or the tumor promoter, 12‐0‐tetradecanoylphorbol 13‐acetate (TPA) to neonatal Swiss Webster S/W (NIH) mice caused precocious tooth eruption. However, TPA, unlike EGF, did not enhance eyelid opening. The response was correlated with the tumor‐promoting activity of various phorbol congeners. Furthermore, TPA‐induced tooth eruption appeared to be prostaglandin‐dependent, whereas EGF‐induced eruption was insensitive to the prostagland

ISSN:0270-3211    

DOI:10.1002/tcm.1770010404

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe in vivo teratogenic potential of valproic acid was evaluated in the CD‐1 mouse. Dose selection was based on the estimated lethality curve and several doses were evaluated. Treatment during early organogenesis (Days 8–10) produced a dose related increase in congenital abnormalities which was accompanied by a decrease in fetal weight, Rib and vertebral abnormalities together with exencephaly were the most common defects. Greater embryo mortality was apparent following teatment during late organogenesis (Days 11–13), but the surviving fetuses were less sensitive to the dysmorphogenic effects and cleft palate was now the most common defect, Early neurula stage mouse (Day 9) and rat (Day 10) embryos were cultured in the presence of valproic acid (0.6–1.8 mM) for 48 hr. There was significant reduction in growth which was accompanied by a variety of dysmorphogenic effects. Irregular segmentation of somites together with incomplete and irregular fusion of brain folds were most evident. These were observed at concentrations of valproic acid where no adverse effects on the yolk sac circulatory system were apparent. These in vitro effects appear to be comparable to the in vivo observations and suggest a direct teratogenic action of valproic acid on the developing rodent

ISSN:0270-3211    

DOI:10.1002/tcm.1770010405

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

年代:1981

数据来源: WILEY

摘要:

AbstractAlphafetoprotein (AFP) binding of estrogens is thought to protect fetal and neonatal rats from the toxic effects of high maternal estrogen levels. Since the plasma concentrations of several other steroid binding proteins are ligand regulated, we tested the hypothesis that estrogens regulate plasma AFP levels. A batch Sephadex equilibrium binding assay and Scatchard analysis were used to quantitate AFP in plasma of both adult mice (C3H/HeN MTV−) chronically fed diethylstilbestrol (DES) or estradiol (E2) and neonatal rats (CD) injected daily with E2for the first 15 days of life. Estrogen treatment of adults did not increase AFP above the nondetectable adult levels, nor did it alter the plasma disappearance curve of neonatal AFP. In both adults and neonates, other estrogen responses were noted, demonstrating that the failure of biologically active estrogens to alter AFP levels is not due to insufficient amounts of estrogen. We suggest that estrogens do not alter patterns of AFP synthesis and degradation in the rat, a finding which contrasts with the general observation that steroids regulate the levels of their binding protein

ISSN:0270-3211    

DOI:10.1002/tcm.1770010406

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

年代:1981

数据来源: WILEY

摘要:

AbstractA direct‐acting alkylating agent, beta‐propiolactone (BPL), was microinjected into eggs of the frog, Bombina orientalis (Anura: Discoglossidae). Response to injected BPL was dose‐dependent. Seventeen or more nmoles of BPL disrupted cortical pigment in the animal hemisphere and completely inhibited cleavage. Ten nmoles of BPL allowed normal cleavage but caused a variety of teratogenic patterns and decreased survivorship at every developmental stage. Small neoplasms were found in several prehatching tadpoles derived from BPL‐microinjected eggs. Responses of diploid and laser‐irradiation‐induced haploid eggs to BPL and ethyl‐methanesulfonate (EMS) were then compared to determine whether or not the induced anomalies could be attributed to genetic (mutational) events; development of the haploid and diploid embryos did not differ. Egg microinjection is not suitable as a mutagenesis assay. However, the technique has potential to reveal insights into nucleocytoplasmic interactions in development, and further analysis of the mode of action of injected alkylating agents, for example, by nuclear transplantation, may provide insights into mechanisms of teratogenesis

ISSN:0270-3211    

DOI:10.1002/tcm.1770010407

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

年代:1981

数据来源: WILEY

摘要:

AbstractTCDD (2,3,7,8‐tetrachlorodibenzo‐p‐dioxin) causes a high percentage of isolated cleft palate in the fetus when administered to the pregnant dam at day 10 of gestation but only in certain strains of mice (ie, C56BL/6J (C57BL)). These strains are also known to have a specific cytosolic receptor protein (Ah‐receptor) in the liver for polycyclic hydrocarbons and TCDD, and respond to these compounds by increased levels of cytochrome P‐450 mediated monooxygenase activities and probably several other enzyme systems. We have shown that midgestational embryos of sensitive strains exhibit high levels of the TCDD cytosolic receptor in the maxillary processes and secondary palatal shelves prior to palate closure. Binding studies and Scatchard plot analysis revealed an apparent Kd of 1.1 nM and a Bmaxof 32 fmole bound TCDD/mg cytosolic protein from C57BL maxillary processes on day 13 of gestation. The TCDD resistant strain, AKR/J, did not show any specific binding of TCDD. Mesenchymal cells from C57BL secondary palatal shelves retained the cytosolic receptor for TCDD when grown in culture. These results suggest that the teratogenic effects of TCDD in sensitive murine strains are dependent upon the binding of TCDD to the cytoplasmic receptor in

ISSN:0270-3211    

DOI:10.1002/tcm.1770010408

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

年代:1981

数据来源: WILEY

摘要:

AbstractCell killing and induction of mutations were studied in V79 Chinese hamster cells and in Escherichia coli WP2 and WP2 uvrA as a result of treatment with four furocoumarins and near ultraviolet light (NUV). The results obtained on V79 Chinese hamster cells showed that the three angelicin derivatives tested have mutagenic as well as cytotoxic activity, although at different levels; 8‐methoxy‐psoralen (8‐MOP), which is the most cytotoxic drug, induces the lowest number of 6‐thioguanine (6‐TG) resistant mutants as a function of surviving fraction. The three angular furocoumarins, 4,5′‐dimethylangelicin, 5‐methylangelicin, and 4′‐hydroxymethyl‐4,5′‐dimethylangelicin, were found not to be bactericidal and only slightly mutagenic in excision‐proficient Escherichia coli. They were much more active in inducing cell death and mutations in Escherichia coli uvrA. On the contrary 8‐methoxypsoralen displayed mutagenic and cytotoxic activity in E. coli WP2 uvr+as well as in E. coli uvrA. This study confirms that (1) mono‐adducts are efficiently repaired in excision‐proficient bacterial strains and (2) the nature of substituents could affect biological properties, such as mutagenic and cyt

ISSN:0270-3211    

DOI:10.1002/tcm.1770010409

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe attachment of tumor cells to plastic surfaces coated with concanavalin A is inhibited by agents that either increase or decrease the apparent microviscosity of the plasma membrane. Since some promoters have been reported to decrease the plasma membrane microviscosity of treated cells, we have tested whether these agents inhibit tumor cell attachment. All 13 promoters tested were found to inhibit attachment at nontoxic concentrations. The apparent microviscosity of treated plasma membrane was reduced in the 11 cases where a measurement was possible. Eight of nine nonpromoting agents did not inhibit attachment. The exception, Aroclor 1254, was inhibitory on prolonged incubation. Finally, 10 of 13 antipromoting agents were found to also inhibit attachment. The apparent membrane microviscosity was increased following treatment with these inhibitory antipromoters. Thus, a consistent feature of promoter and antipromoter treatment is an alteration of the functional and the apparent fluid properties of the plasma membrane. These characteristics may be useful in the design of an in vitro assay for promoting activities in environmental samples.

ISSN:0270-3211    

DOI:10.1002/tcm.1770010410

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

年代:1981

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770010401

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

年代:1981

数据来源: WILEY