α‐fetoprotein and hepatocarcinogenesis in rats fed 3′‐methyl‐4‐(dimethylamino)azobenzene or n‐2‐fluorenylacetamide

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Abstract
Serum α‐fetoprotein (af) of rats during hepatocarcinogenesis by 3′‐methyl‐4‐(dimethylamino)azobenzene (3′‐Me‐DAB) or N‐2‐Fluorenylacetamide (FAA) was checked by the micro‐Ouchterlony method throughout the course of the study. The serum af appeared in two phases, early from the 3rd to 5th week and late during the development of large carcinomas.The frequency of early appearance of serum af varied considerably according to the difference in age, sex, and strain of the animals or the difference in type or dose of the carcinogen. In general, 3′‐Me‐DAB was a much stronger carcinogen than FAA in producing early serum af. A good correlation was observed between the serum af level and the intensity of oval cell proliferation in the liver at this stage.The cell composing the nodular hyperplasia in 3′‐Me‐DAB or the area of hyperplasia in FAA carcinogenesis, which replaced the major part of the liver in the next stage and had been considered the most possible forerunner of the carcinoma, did not seem to produce af.The serum af in the late phase was produced by the carcinoma. The majority of the 3′‐Me‐DAB‐induced carcinomas belonged to the mixed type carcinoma. This type of carcinoma was strongly af‐producing with the required minimal size of 10 mm in diameter for positive serum af. Most of the FAA‐induced carcinomas were of the trabecular type. This type of carcinoma was relatively weak in af‐production and the serum af was negative until a trabecular carcinoma became larger than 20 mm in diameter.The appearance of early serum af was distinct evidence of a fair progress of hepatocarcinogenesis, and a positive correlation was found between the degree of this phenomenon and the frequency of development of a carcinoma producing large amounts of af. However, the appearance of early serum af was not an absolute requisite for later development of carcinomas.