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Bioavailability and Disposition of the Bioactive Food Component D-Limonene, and Implications for Breast Cancer Prevention
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azu_etd_11315_sip1_m.pdf
Author
Miller, Jessica A.Issue Date
2010Advisor
Thomson, Cynthia A.Committee Chair
Thomson, Cynthia A.
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The University of Arizona.Rights
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.Abstract
d-Limonene is a monoterpene found in high concentration in citrus peel oil. Evidence from animal models and cell culture indicate that it has strong anti-cancer effects, particularly in mammary cancer models. Chapter 1; "D-LIMONENE: A BIOACTIVE FOOD COMPONENT FROM CITRUS AND EVIDENCE FOR A POTENTIAL ROLE IN BREAST CANCER PREVENTION AND TREATMENT" is a review paper accepted to Oncology Reviews. This review describes the evidence for d-limonene's anti-cancer mechanisms, bioavailability and safety, focusing on relevance to breast cancer prevention. Chapter 2; "ADIPOSE TISSUE ACCUMULATION OF D-LIMONENE WITH THE CONSUMPTION OF A LEMONADE PREPARATION RICH IN D-LIMONENE CONTENT" is published in Nutrition and Cancer journal and describes a phase I clinical trial in which participants consumed 40 oz of high-limonene lemonade daily. This study demonstrated that after 4 weeks of oral consumption of high-limonene lemonade, d-limonene deposits in high levels in adipose tissue. Chapter 3; "A CLINICAL BIOMARKER STUDY OF TOPICALLY APPLIED D-LIMONENE FOR BREAST CANCER PREVENTION" was submitted to Nutrition and Cancer journal. In this phase 0 clinical study, four weeks of a 10% d-limonene formulation resulted in minimal change in NAF and plasma biomarkers or d-limonene levels. Biomarkers in NAF and plasma, however, were significantly differently correlated with BMI and menopausal status, perhaps suggesting effect modifications. Chapter 4: "MOUSE MAMMARY TISSUE DISTRIBUTION OF D-LIMONENE AND PERILLIC ACID FOLLOWING ORAL AND TOPICAL D-LIMONENE ADMINISTRATION," was a study comparing d-limonene and perillic acid disposition after administration of 10% and 20% d-limonene in coconut oil in topical and oral forms to SKH-1 mice. This study demonstrated that d-limonene deposits in high levels in mouse mammary tissue after both oral and topical administration short-term, but is largely cleared after 24 hours in this model. Perillic acid deposits in high levels in adipose after oral administration, and these high concentrations remained after 24 hours. Chapter 5: "IMPLICATIONS AND FUTURE DIRECTIONS" provides a summary of the key findings from these three projects and proposals for future research. The appendices provide results from smaller d-limonene projects, as well as extensions of the body of the dissertation work.Type
textElectronic Dissertation
Degree Name
Ph.D.Degree Level
doctoralDegree Program
Nutritional SciencesGraduate College