This Date in UCSF History: UC Confirms Cell Behavior

Campus

[Originally published in Synapse - The UCSF student newspaper, Jan. 16, 1959]

Important new evidence on how the nuclei of cells "communicate" with' the material that surrounds them was reported to the American Association for the Advancement of Science by researchers from the University of California Medical Center, San Francisco.

For the first time, they have shown that ribonucleic acid (RNA) moves from the nuclei of human cells into the surrounding cytoplasm. RNA plays a key role in the manufacture of new protein by the cytoplasm, and is thought to be at least one means by which gfenetic material in the nucleus governs the cytoplasm's behavior and characteristics. The new findings strengthen this hypothesis.

The work was reported by Dr. Lester Goldstein, assistant research physiologist, and Miss Julie Micou, laboratory technician. Their studies were done in the Cancer Research Institute at the U.C. Medical Center, using cultures of cells from the amnion, the protective sac that surrounds the fetus before birth.

Dr. Goldstein and other investigators had shown previously that RNA is transferred from nucleus to cytoplasm in amoebae and other primitive organisms. This report, however, directly confirms for the first time that this process takes place in human and other mammalian cells.

The studies were supported by the American Cancer Society and University cancer research funds.

The U.C. researchers used a combination of precision techniques, only recently available, that permit exact localization of radioactive RNA on photographic film. Their measurements showed a distinct, progressive transfer of RNA from nucleus to cytoplasm over .a 24-hour period.

Cells were prepared for study by bathing them in a medium containing cytidine—a substance that enters into nucleic acid formation —that had been labelled with tritium (radioactive hydrogen). The radioactive cytidine rapidly concentrated in the cell nuclei. The cells were then allowed to live for varying periods up to 24 hours before being fixed and "autoradiographed" — placed

under radiation-sensitive photo graphic film.

The longer a cell was allowed to function after being labelled, the more radioactivity concentrated in the cytoplasm and the less remained in the nucleus.

The use of a tritium label allowed this transfer of radioactivity to be recorded with extreme exactness. Since tritium is a form of hydrogen and all organic materials contain large amounts of hydrogen, it can be used to make biochemical substance's extremely radioactive. But its radioactive particles travel only 1/10,000 of an inch, so only those radiations that travel straight up will register on an overlying film.

Dr. Goldstein and Miss Micou incorporated a series of checks into the experimental procedure to assure that the movement of radioactivity into the cytoplasm really represented a transfer of RNA.

To rule out the possibility that the cytoplasm was simply picking up unchanged cytidine, rather than RNA, they let some of the cells grow in a medium containing extra, non-radioactive cytidine that could compete for a place in the cytoplasm. This did not prevent the movement of radioactivity out of the nucleus, indicating that the* cytoplasm was actually receiving nucleic acid.

Before examining the cells for radioactivity, the investigators treated them with an enzyme that destroys DNA, the other principal nucleic acid. (DNA is normally concentrated in the chromosomes of cells and is believed to govern heredity.) This assured that any cytidine that had entered the cells' DNA would be dissipated and that the only source of recorded radioactivity would be RNA. Dr. Goldstein read a paper on the new findings at the 125 th meeting of the AAAS here.