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Bovine Meat and Milk Factors (BMMFs) are circular, single-stranded DNA molecules (cssDNAs) originally found in beef and cow's milk which have been linked to the development of cancer—particularly colorectal and breast cancer.[1] They are formerly known as Slow Progressive Hidden INfections of variable X (SPHINX). Similar molecules have since been found in a much wider range of food.[2]
BMMF/SPHINX sequences are able to copy themselves in animal cells. They encode functional proteins that are expressed in some animal cells. Every BMMF/SPHINX contains at least a "Rep" open reading frame, which encodes a replication endonuclease that, in HEK 293TT cells, acts to replicate and retain the cssDNA.[3]
BMMF/SPHINX sequences are divided into four clades. Clades 1, 2, and 3 share sequence similarity with the plasmids of Acinetobacter baumannii. (A. baumanii regularly produces outer membrane vesicles containing these plasmids, and animal cells are known to take up these vesicles.) Clade 4 shares sequence similarity with Gemycircularvirus.[3]
Health research
The potential connection between BMMFs and cancer has been made based on assessments of epidemiological data[4][5][6] and the investigation of antibodies in human serum.[7][8] Research has also suggested a potential link between BMMFs and neurodegenerative diseases such as multiple sclerosis.[7]
At the end of 2017, evidence was presented that BMMFs in human cells show long-term survival, through the identification of BMMFs' RNA and protein products.[7][9] In February 2019, evidence was presented of a previously unknown infectious agent in the blood serum and milk of Eurasian cattle that could indirectly trigger the development of colorectal cancer.[5]
Abandoned theories
For a short period the SPHINX DNAs were believed to have some connection with transmissible spongiform encephalopathy following its isolation from CJD and scrapies patients.[10] The author of the article has since moved on to a viral hypothesis for TSE.[11]
^Pohl, Sina; Habermann, Diana; Link, Ellen K.; Fux, Robert; Boldt, Christine L.; Franz, Charles M.A.P.; Hölzel, Christina; Klempt, Martin (May 2022). "Detection of DNA sequences attributed to bovine meat and milk factors (BMMF/SPHINX) in food-related samples". Food Control. 135: 108779. doi:10.1016/j.foodcont.2021.108779.{{cite journal}}: CS1 maint: article number as page number (link)
^Manuelidis, Laura (April 2011). "Nuclease resistant circular DNAs copurify with infectivity in scrapie and CJD". Journal of NeuroVirology. 17 (2): 131–145. doi:10.1007/s13365-010-0007-0.
^Botsios, Sotirios; Manuelidis, Laura (August 2016). "CJD and Scrapie Require Agent-Associated Nucleic Acids for Infection". Journal of Cellular Biochemistry. 117 (8): 1947–1958. doi:10.1002/jcb.25495. PMID26773845.
