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Epidermal growth factor (EGF) markedly stimulates cell proliferation in a variety of mammalian systems. For this reason, EGF and factors related to EGF were examined for a possible role in the promotion and maintenance of the uncontrolled growth state that is a characteristic of malignant neoplasias. Phorbol ester tumor promoters, compounds that are capable of promoting tumors in the mouse skin carcinogenesis assay, act synergistically with EGF to stimulate DNA synthesis in cultured fibroblasts despite an inhibitory effect on the binding of EGF to its cellular receptor. Sparing of EGF degradation in combination with recovery of EGF binding was postulated to be responsible for the increased role of DNA synthesis in cells exposed to the phorbol esters. The hypothesis is presented that the hyperplasiogenic component of tumor promotion may be mediated, at least in part, by local alterations in growth factor levels. Recent evidence suggests the existance of a family of molecules related to EGF as defined by the ability to bind to the EGF receptor. These factors (transforming growth factors) appear to be responsible for the phenotypic alterations characteristic of transformed cells. Using a radioreceptor assay, two EGF-like factors were isolated from mouse submaxillary gland. These factors were not transforming growth factors and appeared to be modified EGF molecules. Two EGF-like factors, molecular weight 27,000 and 13,000, were identified in medium conditioned by Rous sarcoma virus (RSV)-transformed cells and were shown to possess the characteristics of a transforming growth factor. In addition, rat fetus extracts contained a 55,000 molecular weight EGF-like factor with the properties of a transforming growth factor. The EGF-effector system may therefore play an important role in embryonic development and in the maintenance of the neoplastic phenotype. The difference in the molecular weights of the RSV-factor and the fetus factor indicates that there are numerous members of the class of EGF-like molecules, and that RSV-transformation probably does not induce the re-expression of a fetal growth stimulatory factor. The results of these experiments suggest that EGF and EGF-like factors are biologically important growth-stimulating molecules that must be tightly regulated to maintain normal physiological conditions.

Modifications of cellular responses to epidermal growth factor (EGF) induced by tumor promoters and anti-promoters were examined. The effect of the promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) EGF binding was studied using mouse epidermal cells. Initially, TPA decreased EGF binding. However, when cells were incubated continuously in TPA plus a low concentration of EGF, more EGF bound to TPA-treated cells than to control cells. It was shown that the effects of TPA were partially reversible and that the greater amount of EGF bound to TPA-treated cells over controls after long-term incubation was due to larger amounts of whole EGF in the media of TPA-treated cells when cells have regained their ability to bind EGF. The ability of TPA to induce DNA synthesis synergistically with EGF may depend on the transient sparing of EGF from degradation and subsequent binding of the spared EGF. Fluocinolone acetonide (FA) and retinoic acid (RA) are potent anti-promoters able to induce increased EGF binding. The possibility that these compounds exerted their anti-promoting activities through offsetting TPA-induced EGF binding alterations was studied. Rat-1 fibroblasts were used to examine the effect of FA on TPA-mediated changes in EGF binding and EGF-induced ornithine decarboxylase (ODC) activity and DNA synthesis. Pretreatment with FA caused increased EGF binding and decreased ODC activity and DNA synthesis stimulated by high or low EGF concentrations. The glucocorticoid lowered ODC and DNA synthesis induced by EGF in combination with TPA to levels closer to control (EGF alone) levels. These data indicated that the anti-hyperplasiagenic effect of FA may be partially mediated through the EGF receptor. The effects of RA on EGF binding and EGF-induced cellular responses were examined in Rat-1 and Swiss 3T3 fibroblasts. Pretreatment with RA resulted in increased EGF binding to 3T3 cells only. However, RA treatment was able to enhance ODC activity in both cell lines. Retinoic acid binding protein was detected only in Rat-1 cells. It was therefore unlikely that the effects of RA on ODC induction were mediated by either altered EGF binding or the presence of CRABP. Experiments with 3T3 cells demonstrated that TPA alone was able to induce ODC activity. It is therefore possible that TPA exerts part of its tumor promoting action through the EGF receptor, but other sites of action also contribute to its promoting properties.

Political communication scholars aim to understand the effect of messages on political attitudes and behavior. Past scholarship has identified three sources of influence in forming attitudes and behavior: affective, cognitive, and personality factors. While much attention has been paid to the impact of each single factor, little research has attempted to integrate them. Using the Affective Intelligence model as a theoretical point of departure (Marcus, & MacKuen, 1993; Marcus et al., 2000), this dissertation explored the simultaneous--and, in some cases, interactive relationships--between these attitudinal and behavioral influences. An experiment was conducted to answer three questions: first, do the causal claims made by Marcus and colleagues regarding the impact of emotion on political attitudes and behavior hold-up outside the realm of survey research? Second, what role does cognitive appraisals of messages play in the political persuasion process? Finally, does political efficacy moderate the relationships between induced emotional response, cognitive appraisals of messages, and political attitudes and behavior? Alternatively stated, does political efficacy link these factors together?The results of this study should be carefully interpreted as the causal instrument underlying manipulated attitudes was not transparent. The desired experimental manipulation--induced anxiety--was not unidimensional. While inductions did induce negative affect, they simultaneously induced positive affect. Within the confines of this document, this result is discussed at length and numerous possible explanations are offered.Structural equation modeling indicated that affect had a small impact on political attitudes and behavior. Likewise, the impact of cognitive appraisals of messages on attitudes and behavior was small. Alternatively, internal efficacy had a substantial main effect--not an interactive effect--on political attitudes and behavior.In summary, the results demonstrated the power of personality in predicting political attitudes and behavior. By trait, some individuals are more politically efficacious than others. Those with higher levels of internal efficacy tended to identify experimental messages as relevant to the attitudes they held, indicating that confidence in one's ability to comprehend politics and understand political happenings leads to identifying message content as applicable or appropriate. Additionally, these same individuals were likely to seek out more information about politics.

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