In an effort to obtain evidence for or against the existence of a humoral factor controlling hepatic regeneration, observations in over 800 rats have resulted in the following: (a) Plasma obtained from hepatectomized donors injected into normal rats either intravenously or intraperitoneally resulted in an increase in mitoses of similar magnitude to that observed when plasma from normal donor rats was injected. No significant increase in hepatic DNA synthesis as determined by incorporation of P32 into DNA resulted when either route of administration was employed. (b) Serum obtained from hepatectomized normal and cirrhotic rats and injected intravenously or intraperitoneally failed to significantly increase mitoses. DNA-phosphorus specific activity was no greater than that observed following the injection of normal serum. (c) With a variety of time relationships between hepatectomy, P32 injection, and sacrifice of animals, no definite evidence of increased DNA synthesis in the intact normal member of a parabiotic pair occurred following hepatectomy in the other which was either normal or cirrhotic. Likewise, no effect upon mitoses in the intact member was observed. Following sham operation in parabiotic rats an increase in mitoses was not seen.

It is concluded from these experiments that these is no unequivocal evidence to support the concept that a specific humoral factor is present in the serum or plasma of hepatectomized animals which, when injected into normal animals, influences hepatic parenchymal cell activity. Nor is there significnat evidence that hepatectomy in one member of a parabiotic pair affects liver cells of the other member in this regard. The great variation in the number of mitoses encountered in all experiments performed tends to minimize the value of this parameter as an index of hepatic parenchymal response to a specific factor.

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Supported by U.S.P.H.S. Grants #AM-04651-03 and #AM-00369-12.

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