Administration of polycyclic hydrocarbons to rats is followed by an increase in the activities of several of the mixed function oxidases present in the liver. Under certain conditions polycyclic hydrocarbons are metabolized by these enzymes to metabolites of high carcinogenic potency ( 1 ) . The development of tumors induced by chemical carcinogens is subject to some elements of endocrine control (2-4), but the mechanisms by which endocrine factors affect chemical carcinogenesis are not understood. I t remains a possibility that during the early phases of carcinogen-tissue interaction hormones modify the metabolic activity of liver and thus increase or decrease the extent of metabolic modification of administered polycyclic hydrocarbons. The effective level of proximate carcinogens or the modification of the interaction between carcinogen and macromolecules of liver nuclei may be among the biochemical parameters which can be affected by hormones. In the present investigation, we have studied some of the initial phases of the interaction of 7,12-dimethylbenz [a] anthr a~e n e -~H (DMBA) and of benz [ a ] -anthra-~e n e -~H (1,2-BA) with hepatic DNA and histones from intact and gonadectomized male and female rats.MateriaZs and Methods. Intact and gonadectomized male and female Sprague-Dawlrey rats (180 to 200 g) were used throughout the experiments. The time lapse between operation and killing was 2 1 days. The animals were guillotined, after which the livers were cannulated and perfused with ice-cold 0.9% NaCl. Slices were prepared by means of a Stadie-Riggs microtome. The slices (500 mg of wet wt) were placed in a 25-ml Erlenmeyer flask and suspended in 5 ml of 0.05 M sodium phosphate buffer, pH 7.9, containing 2 pCi of 7,1%-dimethylbenz-[~Ianthracene-~H (G) (sp act 750 pCiJ mmole), or 2 pCi of benz[~]anthracene-~H (G) (sp act 750 pCi/mmole) dissolved in 0.1 ml of propylene glycol. Incubations were carried out at 37" in a Dubnoff metabolic incubator in air. At the end of the incubation time the slices were removed from the incubation medium and washed 5 times in 4 ml of ice-cold 0.05 M sodium phosphate buffer, pH 7.9, containing the respective nonradioactive carcinogens (dissolved in propylene glycol) at a concentration of M . The slices were homogenized in 8 ml of 0.05 M sodium phosphate buffer, pH 7.9, containing 0.25 IM sucrose in a Potter-Elvehjem glass homogenizer. The nuclear fraction was isolated and purified by sedimentation through 2.3 M sucrose as described previous-For the isolation of the total histone fraction, nuclei were extracted for 6 hr with three 5-ml portions of ice-cold 0.25 N HCl (6).The combined acid extract was clarified by centrifugation and contained the total acidextractable histone fraction. DNA was extracted from the purified nuclei by a modification of the Kirby procedure (7). DNA was determined with diphenylamine (8). Protein was determined by the method of Lowry et al. (9). For the determination of radioactivity, the samples were dissolved in 2 ml of NCS solubilizer (NCS Tissue Sol...