RESPONSE IN MACROMOLECULAR SYNTHESES OF MOUSE L CELLS TO BLEOMYCIN, WITH SPECIAL REFERENCE TO CELL-ANTIBIOTIC INTERACTION

The inhibitory effect of bleomycin on DNA, RNA and protein syntheses of mouse L cells was determined. DNA synthesis was most affected. Protein and RNA syntheses were less affected in this order. Inhibition of DNA synthesis exhibited an upward-concave curve as a function of time of exposure to bleomycin. Analysis of this particular curvature revealed a characteristic interaction between the antibiotic and mammalian cells. Results obtained from the experiments of two pulsed drug treatments showed that (1) when bleomycin was introduced into culture, cell resistance developed with time and was complete within 60 minutes, and (2) the resistance so induced disappeared in approximately 2 hours upon removal of bleomycin. The nature of this resistance was not elucidated. Either an enzyme which inactivates bleomycin or DNA-repair enzymes may be responsible for resistance. The above interaction may have some relevance to bleomycin chemotherapy.