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.

Highlights

  • Summary.-Female rats were maintained on standard laboratory diet, Miller's diet or Miller's diet containing 3'MeDAB

  • Alpha-foetoprotein was not detected in over 1400 urine specimens obtained from rats fed the standard laboratory chow or Miller's diet

  • Using the double immunodiffusion technique, AFP was occasionally detected in the concentrated urine of an rats as early as the 4th week of the animal the serum of which was negative. experiment, whereas it was not found in During the follow-up of rats fed the the serum prior to the 4th month

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Summary

MATERIALS AND METHODS

Animals.-Female albino rats of the Hebrew University (Sabra) strain, aged 60 days at the beginning of the experiment, were used. Following absorptions with lyophilized blood and an organ pool of healthy adult rats, the antisera to AF and ES were found to contain one and two precipitating antibodies, which 'were specific for AFP and for AFP plus alphamacrofoetoprotein (AMFP) respectively (Boss, Dishon and Rosenmann, 1975). Collection and testing of urine and serum samples-.The rats were put in metabolism cages over urine-faeces separators and 24 h urine samples were collected from individual animals at 2- to 4-week intervals. A specimen giving one precipitin line with anti-AF antiserum and two bands with anti-ES antiserum was considered to contain AFP as well as AMFP. Urine containing AFP produced a single line when tested with either antiserum, since the high molecular weight AMFP does not pass the normal glomerular filter (Rosenmann et al, 1974b). All the data were collected on IBM cards and the computations were made after termination of the experiments

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