Studies on Serum Protein Changes during 3'-Methyl-4-Dimethylaminoazobenzene Hepatocarcinogenesis in Rats. II. Studies on α2-Acute Phase Protein (Weimer) as a Fetoprotein

During the hepatocarcinogenesis of Wistar strain male rats fed with 3'-Me-DAB, changes of Weimer's serum alpha2-acute phase protein (α2-AP) and the mechanism involved were investigated in comparison with alpha-fetoprotein (AFP). The results obtained were as follows: 1) The biochemical properties of α2-AP purified in this study coincided with those reported by other authors. The specific anti-α2-AP serum was prepared and the specificity was identified with reference anti-α2-AP serum donated from H. E. Weimer. Determinations of serum α2-AP and AFP levels were carried out by Mancini's single radial immunocliffusion technique. 2) Serum α2-AP levels were found to increase transiently in parallel with the initial elevation of AFP, and increased gradually again after 8th week of feeding and was elevated markedly after the liver carcinoma appeared. In the latter stage, α2-AP levels were correlated significantly with AFP levels in rat sera and with the tumor size. 3) In immunohistological studies, α2-AP was detected in the cytoplasm of part of the oval cells and many small or mature hepatocytes. Findings in carcinomatous regions revealed that α2-AP was localized in the cytoplasm of hepatoma cells in various histological aspects of the tumor. 4) When the synthesis of α2-AP was examined by the in 't i/ro culture method of Hochwald, it was found that hepatoma tissues produced much larger amounts of α2-AP than the non-carcinomatous counterparts of the liver. Experiments with nude mice transplanted with rat hepatoma showed an occurrence of both rat α2-AP and AFP in their sera. These results indicated that serum α2-AP was derived from multiple sources of tissues but more largely from hepatoma tissues than non-carcinomatous regions. It was considered that the mechanism of increased serum level may he different to some extent between α2-AP and AFP