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Isoleucine-mediated Regulation of Genome Replication in Various Mammalian Cell Lines¹

Biomedical Research Group, Los Alamos Scientific Laboratory, University of California, Los Alamos, New Mexico 87544

When suspension cultures of Chinese hamster cells (line CHO) are grown in isoleucine-deficient F-10 medium supplemented with dialyzed sera, the entire population of cells accumulates in a state of G₁ arrest within 24 to 36 hr. Merely by the adding back of isoleucine, the entire population initiates DNA synthesis and subsequently divides in synchrony. This phenomenon is not readily observed in cells infected with pleuropneumonia-like organisms. Cultures of mouse L and Syrian hamster BHK21 cells also accumulate in G₁ under conditions in which isoleucine is specifically depleted from the culture medium, and, upon addition of isoleucine, synthesis of DNA and resumption of cell-cycle traverse commence in synchrony. These results suggest that isoleucine-mediated regulation of genome replication may be a generalized phenomenon in mammalian cells. Speculations are presented regarding possible roles for isoleucine (or its derivatives) in initiation of genome replication.

¹ This work was performed under the auspices of the U. S. Atomic Energy Commission.

² Recipient of NIH Postdoctoral Fellowship 1-F02-CA43809-01 from the National Cancer Institute.

Received 7/10/70. Accepted 9/18/70.

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