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Polyadenylic Acid Content and Electrophoretic Behavior of in Vitro Released RNA's in Chemical Carcinogenesis¹

The Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology, University of Washington, Seattle, Washington 98195

Cytoplasmic RNA from control and thioacetamide-intoxicated rat livers was compared with regard to components separated by polyacrylamide electrophoresis and for the proportion containing polyadenylic acid segments. A further comparison was made with the RNA's released from rat liver nuclei in vitro. Exposure in vivo to thioacetamide was associated with more cytoplasmic RNA's with migrations of 9 to 16 S and with both an acute and prolonged increase in the relative quantity of polyadenylic acid-containing polyribonucleotides. Incubation of control nuclei in vitro was associated with a leakage of approximately 1 to 2% of nuclear RNA with a major migration band at 9 S. Addition of adenosine 5'-triphosphate increased the transport 20-fold, and 9 and 16 S species were transported as well as a 4 S group. Following exposure to thioacetamide, an enhanced "leakiness" released 9 S RNA. Addition of adenosine 5'-triphosphate doubled the quantity of released RNA, which consisted of 9 and 4 S species. Both leaked and adenosine 5'-triphosphate-transported RNA's contained polyadenylic acid segments in roughly 20% of the macromolecules. These studies extend the observation of less stringent control of RNA release and transport in carcinogen exposure and suggest the potential usefulness of the in vitro release system for assaying cellular regulatory phenomena.

¹ These studies were supported in part by USPHS Grants CA 13900 and GM 13540.

Received 6/ 2/75. Accepted 11/12/75.