Tissue sites of alpha fetoprotein synthesis by the rat during pregnancy and hepatoma growth

Abstract

The tissue sites of alpha1 fetoprotein (AFT) synthesis by the rat during gestation and hepatoma growth were determined by specific incorporation of a radiolabeled amino acid precursor into AFP by tissue cultures in vitro. During gestation, AFP were produced by the yolk sac, the fetal liver, and in small amounts by the fetal gastrointestinal tract; there was no synthesis by maternal rat tissues. During growth of a transplantable hepatoma, only the hepatoma tissue synthesized AFP; the nontumor tissue of the host contained AFP but did not produce it.

PIP: Alpha fetoprotein (AFP) synthesis by adult rats during gestation and hepatoma growth was determined in vitro with specific precipitations of radiolabeled AFP antisera after incubation of Spinner cultures of various rat tissues in arginine-free culture medium containing radiolabeled arginine. In general, AFP was synthesized by fetal liver, yolk sac, small intestine, and transplantable (tumor) tissue; none of the normal adult tissues, including testis or ovary, produced AFP. AFP synthesis (measured over 22 hours) was confined to the fetal liver (367 ng), yolk sac (1,368 ng), and to a small extent, the gastrointestinal tract during 19-day gestation. None of the maternal tissues produced AFP. When measured during growth of a transplantable hepatoma, AFP was synthesized only by the hepatoma tissue, though the nontumor tissue of the host contained AFP, due to release of AFP from the cultured tissue as it degenerated in vitro, but did not produce it (noninvolved tissues of hepatoma-bearing rats did not incorporate labeled arginine into AFP in vitro). Identifying fetal organs responsible for AFP synthesis explains observed AFP concentration changes in the postpartum period in rats, since elevated AFP in the mother is caused by AFP produced by the fetus which crosses the placenta or yolk sac to maternal circulation. Elevations above normal (.06 mcg/ml) adult rat concentrations occur in 3 circumstances in the nonpregnant rat: 1) development of AFP-producing tumors; 2) proliferation by normal liver cells; and 3) exposure to chemical carcinogens.