PMID- 222456 OWN - NLM STAT- MEDLINE DCOM- 19790917 LR - 20190705 IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 16 IP - 2 DP - 1979 Feb TI - Integration of the DNA of mouse mammary tumor virus in virus-infected normal and neoplastic tissue of the mouse. PG - 333-45 AB - We have used restriction endonucleases which cleave the DNA of mouse mammary tumor virus (MMTV) at one site (Eco RI) and several sites (Pst I, Sac I and Bam HI) to study infection and mammary tumorigenesis in mice. Proviruses acquired during infection of BALB/c mice foster-nursed by virus-producing C3H females can be distinguished from the MMTV proviruses endogenous to uninfected BALB/c mice by the nature of the fragments generated with Pst I and Bam HI. Using this assay, we show that lactating mammary glands as well as mammary tumors from BALB/cfC3H mice have acquired MMTV DNA, and that a minimum of approximately 10% of normal glandular cells can be infected. The new proviruses appear to be linked to cellular DNA of mammary tumors and infected lactating mammary glands within a limited region (0.2 x 10(6) daltons) of the viral DNA; the location of this region, based upon mapping studies with unintegrated MMTV DNA, suggests that the orientation of these proviruses is colinear with linear DNA synthesized in infected cells and thus approximately colinear with the viral RNA. Comparisons of many mammary tumors and studies of lactating mammary glands with a high proportion of independently infected cells indicate that a large number of sites in the cellular genome can accommodate a new provirus; the acquired proviruses are rarely, if ever, found in tandem with each other or with endogenous proviruses. We cannot, however, distinguish between random integration and integration into a large number of preferred sites in the host genome. Since Eco RI and Bam HI cleavage of DNA from each mammary tumor generates a unique set of viral-specific fragments, we propose that the tumors are composed principally of cells derived from a subset of the many infected cells in a mammary gland; this proposal is supported by our finding that Eco RI digestion of DNA from several transplants of a primary tumor yields the pattern characteristic of the primary tumor. FAU - Cohen, J C AU - Cohen JC FAU - Shank, P R AU - Shank PR FAU - Morris, V L AU - Morris VL FAU - Cardiff, R AU - Cardiff R FAU - Varmus, H E AU - Varmus HE LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (DNA, Neoplasm) RN - 0 (DNA, Viral) RN - 9007-49-2 (DNA) RN - EC 3.1.21.- (DNA Restriction Enzymes) SB - IM MH - Animals MH - Base Sequence MH - *Cell Transformation, Viral MH - Clone Cells/microbiology MH - DNA/metabolism MH - DNA Restriction Enzymes/metabolism MH - DNA, Neoplasm/*metabolism MH - DNA, Viral/*metabolism MH - Female MH - Lactation MH - Mammary Glands, Animal/*microbiology MH - Mammary Neoplasms, Experimental/*microbiology MH - Mammary Tumor Virus, Mouse/*metabolism MH - Mice MH - Pregnancy EDAT- 1979/02/01 00:00 MHDA- 1979/02/01 00:01 CRDT- 1979/02/01 00:00 PHST- 1979/02/01 00:00 [pubmed] PHST- 1979/02/01 00:01 [medline] PHST- 1979/02/01 00:00 [entrez] AID - 0092-8674(79)90010-2 [pii] AID - 10.1016/0092-8674(79)90010-2 [doi] PST - ppublish SO - Cell. 1979 Feb;16(2):333-45. doi: 10.1016/0092-8674(79)90010-2.