Cell killing by actinomycin D in relation to the growth cycle of chinese hamster cells.
Using Chinese hamster cells in culture, we have measured the effectiveness of actinomycin D to suppress division as a function of the position, or age, of a cell in its growth cycle. Cells were first exposed to millimolar concentrations of hydroxyurea in order to produce a synchronized population just before the onset of DNA synthesis. Thereafter, the survival response after 30 min exposures to actinomycin D was measured. Cells become resistant as they enter the S phase and then sensitive again in the latter part of S. When they reach G(2) (or G(2)-mitosis) they are maximally resistant; at 1.0 microg/ml, for example, the survival in G(2) is 30-fold greater than it is in G(1). These results, plus measurements reported earlier on the interaction of damage in S cells due to actinomycin D and X-irradiation, suggest that the age-response pattern of the toxic effects of this drug probably reflects both the functional capacity of DNA-actinomycin complexes and the ability of this antibiotic to penetrate chromatin and bind to DNA.
D000818:Animals; D002455:Cell Division / Q000187:drug effects* / Q000528:radiation effects; D002460:Cell Line; D006224:Cricetinae; D046508:Culture Techniques; D004247:DNA / Q000096:biosynthesis*; D003609:Dactinomycin / Q000494:pharmacology*; D006918:Hydroxyurea / Q000494:pharmacology; D008168:Lung; D008938:Mitosis / Q000187:drug effects / Q000528:radiation effects; D011830:Radiation Effects; D013997:Time Factors
D003609:Dactinomycin; D004247:DNA; D006918:Hydroxyurea