Tissue binding of 2-acetylaminofluorene in BAlB/c and C57Bl/6 mice during chronic oral administration

Blood and tissue binding levels of [9-14C]2-acetylaminofluorene ([9-14C]2-AAF) administered in the diets of female BALB/c and C57Bl/6 mice, were determined. Blood and liver levels reached a plateau after 2--4 weeks, while levels in bladder tissue continued to increase. Binding levels two weeks administration were determined in liver, bladder, kidney, lung, spleen, heart and skeletal muscle. In every instance the binding was linear over a dose range of 0.5--500 ppm 2-AAF. Removal of the 2-AAF in the diet after 48 weeks resulted in a rapid loss of radioactivity from blood and liver, with little or no loss from bladder tissue. The linear dose-response relationship of tissue binding correlated well with the previously reported linear dose response curve for liver tumors but did not correlated with the reported non-linear dose response curve for bladder tumors. A reversed correlation was found in the ability of the tissue to remove bound fluorene residues and the observed rate of tumor occurrence following discontinued administration of the carcinogen.