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Studies on Chromatin

II. Effects of Carcinogens and Hormones on Rat Liver Chromatin

National Cancer Institute, NIH, Bethesda, Maryland

Nuclei were isolated from rat liver during the prolonged feeding of the 2 carcinogens, N-hydroxy-2-acetylaminofluorene and 3'-methyl-4-dimethylaminoazobenzene, and during the prolonged feeding of the noncarcinogen, 2-methyl-4-dimethylaminoazobenzene. Nuclei were also isolated from rat liver tumors induced by the above carcinogens. Chromatin was isolated from these nuclei and analyzed for RNA, total protein, and histone protein content. The 2 carcinogenic diets caused an initial decrease in the RNA content of liver chromatin, while in the resultant tumors the RNA content of chromatin was greatly increased. Total protein content of chromatin from the animals fed the carcinogens also showed significant variations from normal. Neither the RNA nor the total protein content of chromatin from animals fed 2-methyl-4-dimethylaminoazobenzene differed from normal. No significant changes were observed in the histone protein content of chromatin from any animals.

In short-term experiments, N-hydroxy-2-acetylaminofluorene, 3'-methyl-4-dimethylaminoazobenzene, and the carcinogen, aflatoxin B₁, all caused a drop in the RNA content of the nucleus; 2-methyl-4-dimethylaminoazobenzene did not lower nuclear RNA content.

Intense stimulation of the liver by pituitary hormones increased the RNA and total protein (but not the histone protein) content of liver chromatin.

Received 4/11/66. Accepted 6/28/66.