Induction by herbimycin A of contact inhibition in v-src-expressed cells.
Herbimycin A, an inhibitor of pp60src tyrosin kinase, caused src oncogene-expressed cells to become sensitive to contact inhibition, but did not affect ras oncogene-expressed cells. The cell lines tested were temperature sensitive v-src- and temperature sensitive v-ras-integrated nontransformed rat kidney cell line (NRK) (srctsNRK and rastsNRK, respectively) and a wild-type v-src-integrated NIH3T3 (src3T3). srctsNRK cells in densely populated cultures (plated at 1.25 x 10(4) cells/cm2), grown at 33 degrees C in the presence of 0.45 micrograms/ml of herbimycin A, ceased the cell cycle at the G0-G1 stage within 2 days, and the cells showed normal morphology. Upon removal of herbimycin A, the quiescent cells resumed the cell cycle in concert with morphological alteration from 'normal' to 'transformed', and proceeded through the S and M stages successively in a synchronized manner. Cells in the late S stage, compared with those in other stages of the cell cycle, were more sensitive to the killing effect of 5-fluorodeoxyuridine. Such synchronism of the cell cycle was not observed with sparsely populated cultures (2.5 x 10(3) cells/cm2); the cells resumed their asynchronous growth after removal of herbimycin A, although their morphology returned to 'transformed' as in the experiment with the densely populated cultures. The induction by herbimycin A of contact inhibition in densely populated cultures was also observed with src3T3 (grown at 37 degrees C) but not with rastsNRK (grown at 33 degrees C).
Suzukake-Tsuchiya
K
K
Showa College of Pharmaceutical Sciences, Tokyo, Japan.
Moriya
Y
Y
Hori
M
M
Uehara
Y
Y
Takeuchi
T
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001358:Avian Sarcoma Viruses / Q000187:drug effects; D016227:Benzoquinones; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003260:Contact Inhibition / Q000187:drug effects*; D047029:Lactams, Macrocyclic; D015688:Oncogene Protein pp60(v-src) / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D017828:Rifabutin / Q000031:analogs & derivatives
D000900:Anti-Bacterial Agents; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D015688:Oncogene Protein pp60(v-src)