Ultrarapid recovery from lethal effects of bleomycin and gamma-radiation in stationary-phase human diploid fibroblasts.
An ultrarapid phase of cellular recovery, as measured in liquid holding type experiments, was studied in stationary-phase human fibroblasts exposed to bleomycin or cobalt-60 gamma-irradiation yielding comparable levels of cell killing. This rapid recovery was both faster and considerably greater in magnitude after bleomycin treatments. Bleomycin survival curves were multiphasic, indicating the presence of treated cells with varying sensitivities either at the beginning of treatments or as a result of resistance which developed during the treatment period. The amount of both ultrarapid (within 2 to 10 min) and slower recovery was dose dependent after irradiation with 200 to 800 rads or 30-min exposures to bleomycin (5 to 100 micrograms/ml). Following bleomycin treatments resulting in surviving fractions of 1 to 2%, survival increased up to 8-fold after only 2 min of posttreatment incubation. This rapid increase in survival was followed by a slower increase over time periods up to 3 h. In contrast, the rates of cellular recovery after gamma-irradiation were more gradual from 0 to 3 h. Recovery at all posttreatment intervals was always greater after bleomycin than after gamma-treatments, following doses yielding 1 to 50% survival. The ultrarapid component of cellular recovery after bleomycin treatments may have implications for both clinical cancer management and cellular studies directed toward determining mechanisms of action of bleomycin.
Moore
C W
CW
Malcolm
A W
AW
Tomkinson
K N
KN
Little
J B
JB
D001761:Bleomycin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D002478:Cells, Cultured; D004260:DNA Repair / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D007700:Kinetics; D013997:Time Factors
D001761:Bleomycin