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  • Title: Elevated concentrations of serum alpha-fetoprotein in rats with chemically induced liver tumors.
    Author: Kroes R, Sontag JM, Sell S, Williams GM, Weisburger JH.
    Journal: Cancer Res; 1975 May; 35(5):1214-7. PubMed ID: 47266.
    Abstract:
    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. Based on findings suggested by data in humans, this study attempted to determine whether aflatoxin Bl (AFB1)-induced liver tumors in rats produced alpha fetoprotein (AFP) and whether the animal's age influenced such appearance. Other liver carcinogens such as N-hydroxy-N-2-fluorenylacetamide (h2-FAA), N-2-fluorenylacetamide (2-FAA), and diethylnitrosamine (DENA) were tested for their abilities to induce liver tumors which produced AFP. The presence of AFP in serum was determined by double diffusion in agarose and by comparison also with quantitative radioimmunoassay. Male Fischer 344/CS rats were used in all experiments. By double diffusion, the AFP was detected in a majority of tumor-bearing rats that had received either 2-FAA or h2-FAA. Sera of DENA-treated rats with hepatic tumors were all positive, whereas sera of rats with AFB1-induced tumors were positive only in a few cases. However, all sera of tumor bearing rats examined had elevated AFP levels when measured by radioimmunoassay. Still, the average level of AFP in sera of rats bearing AFB1-induced tumors was considerably lower when compared with sera of rats whose tumors were caused by DENA, 2-FAA, or h2-FAA. Younger rats suffered more severe alterations: 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, histological grade of differentiation of induced tumors did not seem to influence the AFP level, although the DENA-treated rats usually had high levels of AFP and less differentiated tumors.
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