Early Elevation of α₁-Fetoprotein in N-2-Fluorenylacetamide Hepatocarcinogenesis

Summary

Utilizing a radioimmunoassay capable of detecting ng quantities of circulating rat α₁-fetoprotein, we examined the induction of this protein by N-2-fluorenylacetamide. Extremely small quantities of N-2-fluroenylacetamide, approximately 1% of a carcinogenic dose, caused a rapid and significant elevation of α₁-fetoprotein that persisted for a considerable period after removal of the carcinogen from the diet. Although the most rapid and often highest elevations were achieved in male rats, comparable elevations were eventually demonstrated in female rats of strains that had selective defects in the metabolic activation of the carcinogen. The elevation in all groups preceded any detectable tissue alteration and was apparently unrelated to cell injury or cell division.

We suggest that the increase in circulating α₁-fetoprotein seen after minimal N-2-fluorenylacetamide exposure is the result of a highly selective derepression of protein synthesis that occurs following the formation of a complex between the metabolite(s) of the carcinogen and specific chromatin loci.