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Binding of Chemical Carcinogens to Nuclear Proteins of Rat Liver¹

Department of Biochemistry and Medicine, Northwestern University Medical School, Chicago, Illinois 60611

The binding of N-hydroxy-N-2-fluorenylacetamide-¹⁴C, p-dimethylaminoazobenzene-¹⁴C, and 7,12-dimethylbenz(a)anthracene-³H to histones and acidic proteins of rat liver nuclei was studied. After the injection of the radioactive carcinogens into rats, liver histone fractions F1, F2a1, F2a2, F2b, and F3 were isolated by selective acid extraction. DNA and acidic proteins were extracted with 4 M CsCl at pH 11.6 and 14 and were separated by equilibrium density centrifugation. Histones and acidic proteins were purified by Sephadex chromatography. Maximum levels of bound radioactivity were present in liver histones at 30 to 60 min and in liver nuclear acidic proteins at 60 to 90 min after a single injection of carcinogen. Significant amounts of radioactivity were associated with liver DNA in all experiments. Under the experimental conditions, the hepatocarcinogens N-hydroxy-N-2-fluorenylacetamide-¹⁴C and p-dimethylaminoazobenzene-¹⁴C were bound preferentially to liver histone fractions F2a1 and F2a2, whereas administration of 7,12-dimethylbenz(a)anthracene-³H led to the preferential radioactive labeling of the liver histones F1 and F2b.

There appeared to be some specificity of carcinogen binding by the nuclear proteins, because pretreatment of rats with nonradioactive carcinogen significantly reduced the extent of labeling after injection of the chemically identical radioactive carcinogen. Pretreatment with nonradioactive carcinogen that was chemically different from the injected radioactive carcinogen did not markedly alter uptake of radioactivity observed without pretreatment.

¹ This investigation was supported by Grant P-505 A from the American Cancer Society and in part by the Steroid Hormone Research Fund, Chicago Wesley Memorial Hospital.

Received 7/ 1/71. Accepted 2/ 4/72.