Dynamics of serum alpha-fetoprotein during spontaneous hepatocellular carcinoma development in mice

Abstract

C3H-A vyfB mice have been studied over their normal life span and 69% developed hepatocellular carcinoma (HCC). Forty-seven mice were bled at monthly intervals, and individual serum alpha-fetoprotein (AFP) profiles are presented for 36 animals. Most of these profiles are quite irregular. Sixty percent of the 15 male mice had a transient serum AFP elevation at 5 months, reaching a mean of 289 ng/ml, compared to a mean of 208 ng/ml for those male mice without a transient AFP elevation and a mean of 185 ng/ml in male mice at 2–4 months of age. All of these male mice and others were tested for murine hepatitis virus and found to be negative. Mice with this early AFP peak tended to have a lower incidence of HCC and much lower AFP values later in life than those not having an early peak, but this difference was not statistically significant. Of the mice whose serum AFP concentration exceeded 300 ng/ml beyond 6 months of age, 23% (9/39) experienced a subsequent pronounced decline in AFP, averaging 74% of previous peak values for males and 44% for females. Of the 39 mice evaluated, 35 were autopsied and 50% (4/8) of these “serum AFP regressors” had minicroscopic evidence of lymphocytic infiltration their livers, as compared to 15% (4/27) of the “non-regressors” that had a similar change.