DIFFERENTIAL EXPRESSION OF ALPHA-FETOPROTEIN AND GAMMA-GLUTAMYLTRANSPEPTIDASE IN CHEMICAL AND SPONTANEOUS HEPATOCARCINOGENESIS

  • 1 January 1979
    • journal article
    • research article
    • Vol. 39  (9) , 3495-3501
Abstract
The expression of 2 markers of fetal liver, .alpha.-fetoprotein (AFP) and .gamma.-glutamyltranspeptidase (GGT), was studied in chemical and spontaneous hepatocarcinogenesis in mice. Serum AFP concentration increased within 3 wk from the commencement of feeding of o-aminoazotoluene. This early elevation subsided about 3 mo. after the beginning of the administration of the carcinogen. A new, sustained elevation of the serum AFP level followed at 5 to 6 mo. accompanied by the appearance of liver tumors. In immunofluorescence, some small oval cells and scattered adult-type hepatocytes contained AFP during the early stage of chemical carcinogenesis. During the later phase, AFP was detected in a few of the nodular areas, in solitary hepatocytes and in groups of carcinoma cells. GGT activity in the liver increased within 1 wk after the carcinogen regimen was started, preceding the early increase of AFP production. At the final stage, the chemically induced hepatomas contained about 80 times more GGT than did normal liver. In histochemical staining, proliferating oval cell and small areas of hepatocytes stained for GGT during the early weeks, and later most nodules, small areas of nonnodular parenchyma, and carcinomas contained GGT. During spontaneous carcinogenesis in male C3HeB/FeJ mice, premalignant lesions, accompanied by a slight increase of serum AFP, precede the appearance of liver tumors. No cells staining for AFP were detected during this early stage. Once overt liver cancers had developed, AFP was readily detectable in the tumors and was localized to some but not all carcinoma cells. The corresponding serum AFP levels were highly elevated. In contrast to the high levels of GGT found during chemical carcinogenesis, no elevation of GGT was found in livers at various stages of spontaneous carcinogenesis, including cancers in 8 individual mice. The production of AFP and GGT is not turned on as a single genetic package and these 2 markers differ in their behavior in liver carcinogenesis.