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Identification of single-stranded DNAs from beef products, their replication in human cells and their relationship with breast cancer

Falida, Konstantina

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Abstract

Epidemiological data indicate a potential relation between the consumption of milk and dairy products and the incidence of breast cancer. Particularly, the consumption of milk and dairy products originating from specific cattle species seems to play a significant role in the development of breast cancer. Our group has isolated a number of circular single-stranded DNAs (Bovine Milk and Meat Factors, BMMFs) from bovine sera of healthy cattle and cow milk, as well as from brain and serum samples of patients suffering from Multiple Sclerosis (MS). This project aims at the identification of such episomal DNA agents in commercially available dairy products and milk samples, resulting in the re-isolation of three of the previously identified agents in milk, yoghurt and crème fraiche and the isolation of two novel DNA agents from milk. Additionally, a similar molecule has been identified in a tissue sample adjacent to breast cancer tissue following a High Throughput Sequencing protocol that has been developed as part of this thesis. In addition, our efforts focus on the search for a permissive system for the identified BMMFs. Replication competence of the MS brain isolate MSBI1.176 was shown in two Hodgkin’s Lymphoma cell lines, the L-1236 and L-428, establishing a long-term persistence in human cells. Co-transfection experiments with more than one agent did not show regulatory effects. Additionally, a potential role of N-Glycolylneuraminic acid (Neu5Gc) as receptor for BMMF infection has been suggested, especially since it has already been reported that it acts as receptor for several viruses. However, the experiments performed in this study only showed a slight increase of replication after external addition of Neu5Gc, but they did not serve conclusive results regarding infectivity of BMMFs. Finally, analysis of sera from breast cancer and Hodgkin’s disease patients showed elevated anti-MSBI1.176 Rep immune response in breast cancer patients compared to healthy donors indicating that infection with BMMF related agents could result in neutralizing antibody formation. This study provides information about potential risk factors of bovine origin contributing to the pathogenesis of breast cancer and Hodgkin’s Lymphoma, which could allow for novel therapeutic strategies for fighting these diseases.

Item Type: Dissertation
Supervisor: zur Hausen, Prof. Dr. med. Dr. h.c. mult. Harald
Place of Publication: Heidelberg
Date of thesis defense: 11 December 2019
Date Deposited: 13 Jan 2020 09:27
Date: 2020
Faculties / Institutes: Medizinische Fakultät Heidelberg > Dekanat der Medizinischen Fakultät Heidelberg
Service facilities > German Cancer Research Center (DKFZ)
Subjects: 500 Natural sciences and mathematics
570 Life sciences
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