FOREIGN (M13) DNA INGESTED BY MICE REACHES PERIPHERAL LEUKOCYTES, SPLEEN, AND LIVER VIA THE INTESTINAL WALL MUCOSA AND CAN BE COVALENTLY-LINKED TO MOUSE DNA

Food-ingested foreign DNA is not completely degraded in the gastrointe stinal tract of mice, Phage M13mp18 DNA as a test molecule devoid of h omology to mouse DNA was pipette-fed to or added to the food supply of mice, The fate of this foreign DNA in the animals was followed by sev eral methods, In 84 animals, fragments of M13mp18 DNA were detected in the contents of the small intestine, the cecum (until 18 h), the larg e intestine, or the feces. In 254 animals, M13mp18 DNA fragments of up to 976 bp were found in blood 2-8 h after feeding, In buffer-fed cont rol animals, M13mp18 DNA could not be detected, M13mp18 DNA fragments were traced by PCR in peripheral leukocytes and located by fluorescent in situ hybridization in about 1 of 1000 white cells between 2 and 8 h, and in spleen or liver cells up to 24 h after feeding, but not late r, M13mp18 DNA could be traced by fluorescent in situ hybridization in the columnar epithelial cells, in the leukocytes in Peyer's patches o f the cecum wall, in liver cells, and in B cells, T cells, and macroph ages from spleen, These findings suggest transport of foreign DNA thro ugh the intestinal wall and Peyer's patches to peripheral blood leukoc ytes and into several organs, Upon extended feeding, M13mp18 DNA could be recloned from total spleen DNA into a lambda vector, Among about 2 .5 x 10(7) lambda plaques, one plaque was isolated that contained a 12 99 nucleotide pair fragment (nt 4736-6034) of sequence-identified M13m p18 DNA, This fragment was covalently linked to an 80 nt DNA segment w ith 70% homology to the mouse IgE receptor gene, The DNA from another lambda plaque also contained mouse DNA, bacterial DNA, and rearranged lambda DNA, Two additional plaques contained M13mp18 DNA fragments of at least 641 (nt 2660-3300) or 794 (nt 4640-6433) nucleotide pairs, Th e medical and evolutionary implications of these observations may be c onsiderable.