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2 (Acute Phase)-Globulin Appearing in Malignancy1
Division of Medicine, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, New York 14203, and the Department of Biochemical Pharmacology, School of Pharmacy, State University of New York at Buffalo, Buffalo, New York
Isolated perfused rat livers obtained from animals bearing the Walker 256 carcinosarcoma incorporated leucine-3H and glucosamine-14C into a plasma protein precipitated with a rabbit antiserum specifically directed against rat
2 (acute phase)-globulin. These data are interpreted to indicate that the liver is a site of synthesis and secretory release of this immunologically distinct plasma component in tumor-bearing rats. These data further indicate that the appearance of this particular
2-globulin in the plasma of tumor-bearing animals is a resultant of de novo synthesis by the liver rather than release of preformed and stored globulin.
The
2 (acute phase)-globulin present in liver perfusates from tumor-bearing rats was shown to be immunologically identical with that found in liver perfusates from rats with acute inflammatory reaction to injury.
The addition of actinomycin D to perfusions of liver and whole blood from tumor-bearing rats markedly decreased incorporation of both leucine and glucosamine radioactivity into immune precipitates containing plasma
2 (acute phase)-globulin, but was without demonstrable effect on albumin synthesis. These data are consistent with the conclusion that hepatic synthesis of plasma
2 (acute phase)-globulin is dependent on DNA-directed messenger RNA synthesis and that the half-life of the specific messenger RNA responsible for its synthesis is substantially different from that responsible for plasma albumin synthesis in this system.
To explain the wide variety of diverse physiologic and pathologic conditions known to elicit the appearance of plasma
2 (acute phase)-globulin in animals, it is proposed that hepatic synthesis of this distinct plasma globulin is mediated by the presence of a common mammalian "inducer" substance present in the blood of all such animals regardless of the nature of the original stimulus.
1 A preliminary report has appeared in Proc. Am. Assoc. Cancer Res., 7: 61, 1966, and was presented at the Ninth International Cancer Congress, Tokyo, Japan, October 1966.
Received 12/27/66. Accepted 6/22/67.
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