The carcinogenicity of aflatoxin M1 in rainbow trout.
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Biomedical subjects
Publications and source records attributed to R Kroes.
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The question was examined as to whether immunosuppression in a rat model system would affect the carcinogenic processes leading to tumors in the liver and the large bowel. The protocols were designed to detect an increased incidence or a shorter latent period stemming from a change in immune status. Groups of rats were given injections prior to initiation of the carcinogen regimen and continuously thereafter with a purified gamma fraction of antilymphocytic serum (ALG). Appropriate controls received the gamma fraction of normal rabbit serum or 0.9% NaCl solution. Permanence of skin allografts showed that ALG was an effective immunosuppressive treatment. For liver cancer induction, rats were fed 120 ppm N-hydroxy-N-2-fluorenylacetamide in the diet for 16 weeks, then were continued on control diet. The animals given ALG developed liver tumors at a rate similar to that of controls. For cancer of the large bowel, rats received a single s.c. dose of 7.5 mg azoxymethane per kg per week for 16 weeks and were then held on control diet. With an identical ALG treatment, there were fewer intestinal tumors in the early part of the treatment, because of the important early development of liver angiosarcoma, not seen in control rats given injections of 0.9% NaCl solution. At a later time, the incidence of intestinal cancer was similar in rats on ALG or on 0.9% NaCl solution. Thus, immunosuppression had little effect on the rate of liver tumor formation with a liver carcinogen. Also, ALG led to the precocious development of liver angiosarcomas, but failed to affect intestinal cancer induction in animals given azoxymethane.
The study was undertaken to determine whether aflatoxin B1 (AFB1)-induced liver tumors in rats produced alpha1-fetoprotein (AFP) and whether the age of the animals would influence such as appearance, a finding suggested by data seen in man. Other liver carcinogens (N-hydroxy-N-2-fluorenylacetamide, N-2-fluorenylacetamide, and diethylnitrosamine) were tested for their ability to induce liver tumors producing AFP. The presence of AFP. The presence of AFP in the serum was determined by double diffusion in agarose and by comparison also by quantitative radioimmunoassay. Using double diffusion, AFP was detected in the majority of tumor-bearing rats that had received either N-2-fluorenylacetamide or N-hydroxy-N-2-fluorenylacetamide. Sera of diethylinitrosamine-treated rats with liver tumors were all positive, whereas sera of rats bearing AFB1-induced tumors were positive in only a few cases. However, all sera of tumor-bearing rats examined had elevated AFP levels by radioimmunoassay. Nonetheless, the average level of AFP in the sera of rats bearing AFB1-induced tumors was considerably lower, compared to the sera of rats with tumors caused by diethylnitrosamine, N-2-fluorenylacetamide, or N-hydroxy-N2-fluorenylacetamide. Rats started on AFB1 when 6 weeks old had more mixed liver tumors with neoplastic hepatocytes and bile ducts and higher AFP levels than did rats started at 26 weeks of age. However, the histological grade of differentiation of inducted tumors did not seem to influence the AFP level.
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