Abstract
Female rats were maintained on standard laboratory diet, Miller's diet or Miller's diet containing 3'MeDAB. Animals fed standard or Miller's diet did not excrete alpha-foetoprotein (AFP) in their urine. Early appearance of AFP was demonstrated by examining the urine of rats on the 3'MeDAB regimen. The incidence of positive urine samples was high between the 5th and 7th week of the experiment. It thereafter declined, but from the 3rd month it steadily rose and reached a maximum of 80% at about 10 months. Though urinary excretion of AFP was irregular in individual animals, several positive urine samples were obtained from all rats followed for more than a few months. The urine of 90% of hepatoma-bearing rats contained AFP at the time of killing. The incidence of elevated serum AFP levels as determined by immunodiffusion, increased with the duration of the experiment, but was still only 70 percent in rats fed 3'MeDAB for over 34 weeks. The severity of the hepatic alterations, as well as hepatocytic uptake of [3H]thymidine, increased with time. The serum of animals fed the standard diet was negative, whereas AFP was very infrequently detected in the serum of rats given Miller's hypoprotein diet. The results demonstrate that, in a population exposed to hepatocarcinogenic agent, the recurring detection of urinary excretion of AFP is a useful indicator of the high risk of developing hepatomas.