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Effect of 2-Acetylaminofluorene on the Binding of Epidermal Growth Factor to Microsomal and Golgi Fractions of Rat Liver Cells¹

Departments of Endocrinology and Diabetes [Z. J., D. H., G. B., C. T., A. L.] and of Medical Oncology [B. I. C.], City of Hope National Medical Center Duarte, California 91010

The livers of rats fed the hepatocarcinogen 2-acetylaminofluorene (0.02%) with chow showed a sharp decrease in the binding of epidermal growth factor to microsomes and Golgi fractions. The binding to the latter decreased from 15.3% specific binding per 0.1 mg protein in controls to 9.4% after 2 days and reached a nadir of 0.8% after 21 days. The binding to microsomes decreased from 26.3% specific binding per 0.5 mg protein in the controls to 17.4% after 4 days and reached a nadir of 7.5% after 46 days. The low binding which persisted until the end of the experiment (85 days) was due to the apparent decrease in the number of receptors without significant changes in their affinity. Also, there was only partial recovery in rats fed 2-acetylaminofluorene for 90 to 107 days and taken off the carcinogen for 30 to 75 days. In vitro, neither 2-acetylaminofluorene nor its metabolites hydroxy- and acetoxy-2-acetylaminofluorene significantly decreased epidermal growth factor binding to the isolated microsomal fraction.

¹ This work was made possible in part by Grant CA33572 from the National Cancer Institute.

² To whom requests for reprints should be addressed.

Received 11/28/83. Accepted 4/ 3/84.