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Release of Repetitive Nuclear RNA into the Cytoplasm in Liver of Rats Fed 3'-Methyl-4-dimethylaminoazobenzene¹

Departments of Human Biological Chemistry and Genetics [N. T. P., V. H.] and Pathology [D. S. F.], The University of Texas Medical Branch, Galveston, Texas 77550

Metabolically active 3.5S RNA bound to nonhistone chromosomal proteins is one of the low-molecular-weight nuclear RNA's present in rat liver. The nucleotide sequences of this RNA are copied from repetitive DNA and are found in the chromatin of liver from normal rats. In rats fed 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) for 1, 3, or 10 weeks, approximately 17% of the nucleotide sequences of this RNA is released into the cytoplasm of the liver cells as parts of larger RNA molecules. With continuous feeding of the azocarcinogen, additional sequences of this nuclear RNA are released from the nuclei. After 16 weeks of feeding, approximately 35% of the total nucleotide sequences of this RNA is found in the cytoplasm. No release of this nuclear RNA into the cytoplasm was observed in control animals fed noncarcinogenic aminoazobenzene. The process initiated by the azocarcinogen which leads to the appearance in the cytoplasm of the nucleotide sequences of this RNA is irreversible, and it continues even when the feeding of the azocarcinogen was interrupted after 10 weeks. Toxic effects of the azocarcinogen in the liver cells result in temporary changes in the cell population of the liver. In our system, the largest changes were observed after 10 weeks of feeding 3'-MeDAB when many of the hepatocytes were larger than normal and when the majority of the hepatocytes had enlarged nuclei and an altered appearance of the chromatin. With continuous feeding of 3'-MeDAB, the changes in liver morphology characteristic for animals fed 3'-MeDAB for 10 weeks become less pronounced, and the liver of animals fed 3'-MeDAB for 17 weeks resembled morphologically the liver of control animals. The release of the nucleotide sequences does not appear to be related directly to the morphological changes in the liver observed during the early stages of the feeding of 3'-MeDAB.

¹ Supported by Grant CA 22559 from the National Cancer Institute, Department of Health, Education, and Welfare, and by Robert A. Welch Foundation Grant H-393.

² To whom requests for reprints should be addressed.

Received 5/ 7/79. Accepted 7/25/79.