Sporadic breast cancers are mainly attributable to long-term exposure to environmental factors, via a multi-year, multi-step, and multi-path process of tumorigenesis involving cumulative genetic and epigenetic alterations in the chronic carcinogenesis of breast cells from a non-cancerous stage to precancerous and cancerous stages. Epidemiologic and experimental studies have suggested that various dietary compounds like green tea and grape seed may be used as preventive agents for breast cancer control. In this research, I have developed a cellular model that mimics breast cell carcinogenesis chronically induced by cumulative exposures to low doses of environmental carcinogens. I used the chronic carcinogenesis model as a target system to investigate the activity of dietary compounds at non-cytotoxic levels in intervention of cellular carcinogenesis induced by cumulative exposures to pico-molar 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P). I used various cancer-associated properties like, reduced dependence on growth factors, anchorage-independent growth, increased cell mobility, and acinar-conformational disruption as measurable endpoints of carcinogenesis. The first part (Part-I) of this dissertation focuses on the understanding the breast cancer progression, importance of environmental carcinogens, role of diet in cancer prevention and importance of epithelial to mesenchymal transition and stem-like cells in chronic carcinogenesis. The next three parts (Part II-IV) focus on understanding the role and mechanisms of dietary compounds in prevention of carcinogenesis and stem-like cell properties. Results in part II revealed the green tea extract at bio-achievable concentration can suppress carcinogen-induced cancerous properties. In Part-III, I compared the four major catechins in green tea extract in suppressing chronic carcinogenesis and the results revealed that epicatechin gallate to be most effective. I also identified that short-term exposure to NNK and B[a]P resulted in elevation of reactive oxygen species, ERK pathway activation and induction of cell proliferation and DNA damage, which can be blocked by green tea catechins. Results in Part-IV describe the roles of properties and markers associated with stem-like cells and the epithelial to mesenchymal transition induced by chronic carcinogenesis and their suppression by green tea catechins and grape seed proanthocyanidin extract. The last section (Part-V) summarizes the findings with their importance and discusses future directions.

The effect of portion size on food intake is a well-documented phenomenon: when served larger portions, individuals significantly increase their food intake. Insofar authors have limited their research on presenting the potential outcomes, while identifying several conditions favorable to this phenomenon. Indeed, the mechanisms of this effect are poorly understood and no research has insofar provided conclusive evidence regarding the underlying mechanism that could help explain the portion size effect. The first part of this dissertation aimed to fill this gap. We argue that the anchoring and adjustment heuristic accounts for most of the favoring conditions evidenced in earlier research and present it as a possible mechanism underlying the portion size effect. In this view, the portion size served is used as an anchor whereas other influences (i.e. economical, metabolic, regulatory, physiological, sensory, social and environmental) may further contribute to adjust total amount of food consumed. Moreover, we argue that prevention strategies based on this decision making literature may be similarly effective to limit excess food intake from enlarged portions. <p><p>The second and third chapter of this dissertation focus on two other factors related to the portion size of foods, namely the container size and the structure of the portion (i.e. food item size). The discussion of this dissertation reviews the facilitating conditions put forward previously to understand the portion size effect, as well as those reinforcing this effect, and how they may be integrated in an anchoring and adjustment perspective of eating. Finally, it aims to provide a food intake model that may accommodate for most environmental influences, with a special focus on the three influences mentioned above. / Doctorat en Sciences Psychologiques et de l'éducation / info:eu-repo/semantics/nonPublished