Bovine Meat and Milk Factors (BMMFs): Their Proposed Role in Common Human Cancers and Type 2 Diabetes Mellitus

Abstract

Exemplified by infections with bovine meat and milk factors (BMMFs), this manuscript emphasizes the different mechanistic aspects of infectious agents contributing to human cancers by "direct" or "indirect" interactions. The epidemiology of cancers linked to direct carcinogens (e.g., response to immunosuppression) differs from those cancers linked with indirect infectious interactions. Cancers induced by direct infectious carcinogens commonly increase under immunosuppression, whereas the cancer risk by indirect carcinogens is reduced. This influences their responses to preventive and therapeutic interferences. In addition, we discuss their role in colon, breast and prostate cancers and type II diabetes mellitus. A brief discussion covers the potential role of BMMF infections in acute myeloid leukemia.

Keywords: bovine meat and milk factors (BMMF); chronic zoonosis; indirect carcinogenesis.

Figure 1

Mechanisms by which infections contribute to human cancer development. BMMFs (bovine meat and milk factors) represent small single-stranded circular DNA, predominantly isolated from sera and dairy products of Eurasian cattle and subsequently identified in periglandular cells of colon, breast and prostate cancers [6]. These infectious agents share characteristics of both bacterial plasmids and known viruses [9], and are related to two DNA isolates from transmissible spongiform encephalopathies reported by Manuelidis [10].

Figure 2

Present knowledge concerning BMMFs (molecular and immunologic evidence).

Figure 3

Typical staining pattern of cells expressing the BMMF replication protein, surrounding Lieberkühn crypts of a colon cancer biopsy at 20× and 40× magnification. Photos provided by Timo Bund.

Figure 4

(A) Lamina propria cells surrounding Lieberkühn’s crypts of the colon, staining positive with monoclonal anti-Rep antibodies. (B) Schematic representation of active sites of inflammation-caused oxygen radical activity indicated by white arrows pointing to blue stars. (C) Experimental confirmation staining of Rep-positive lamina propria cells with antibodies directed against 8-hydroxy-guanosin as a marker for oxygen radical activity (yellow staining). Reproduced [6] with permission.

Figure 5

Sequence of events leading to malignant growth in colon. Uptake of two components is required for binding of infectious particles of bovine meat and milk factors (BMMF) to Neu5Gc as a terminal component of lectin receptors. Both are commonly present in Eurasian bovine sera and dairy products. EM—electron microscopy.

Figure 6

Colon polyps stained with anti-Rep and anti-CD68 monoclonal antibodies. The continuation of inflammation alongside mutagenic activity is evidenced by CD68 presence and Rep expression.

Figure 7

Reduced breast cancer risk after multiple deliveries and breast-feeding periods. Slightly less impressive reductions exist for colon and endometrial cancers (adapted with permission from [6]).

Figure 8

Cytidine monophosphate-N-acetylneuraminic acid hydrolase (CMAH).

Figure 9

Significance of inflammatory events for specific human cancers, e.g., aspirin, ibuprofen and other Cox-2 inhibitors. Copied from [6] with permission.

Figure 10

Cancers increased in type II Diabetes mellitus patients (summarized from [46]). The right lower part (red arrows) of the figure shows vesicular pleomorphic structures labelled with Rep antibody-coated gold particles, suspected to represent BMMF-structures.

Figure 11

Several potential and established preventive interventions for colon cancer in comparison to possible preventions of BMMF infections.

Figure 12

Basal cell carcinoma emerged in a pox vaccination scar. Copied [7] (with permission).

Figure 13

Global epidemiological incidence of AML and colon cancer in comparison to gastric and liver cancers.