Damaging action of photodynamic treatment in combination with hyperthermia on transmembrane transport in murine L929 fibroblasts.
Photodynamic treatment of murine L929 fibroblasts with hematoporphyrin derivative caused inhibition of the 2-aminoisobutyric acid transport system. This was reflected by an increase in the apparent Km with a constant Vmax, indicating impairment of the carrier function rather than a decrease of the number of transport sites. Hyperthermic treatment of these cells resulted in a moderate decrease of the activity of the 2-aminoisobutyric acid transport system. Overall protein synthesis was severely inhibited both by photodynamic treatment and by hyperthermia. Hyperthermia subsequent to photodynamic treatment resulted in an additive inhibition of 2-aminoisobutyric acid transport and of protein synthesis. After photodynamic treatment both 2-aminoisobutyric acid transport and protein synthesis were repaired. The repair of 2-aminoisobutyric acid transport depended on protein synthesis, as shown by the virtually complete blockage of repair by anisomycin. After hyperthermia (either alone or subsequent to photodynamic treatment), no recovery of 2-aminoisobutyric acid transport was observed, although protein synthesis was restored to the initial level. Apparently, hyperthermia subsequent to photodynamic treatment blocks the repair of photodynamically induced damage of this transport system. The experimental results further indicate that protein synthesis is not the rate-determining step for the repair of 2-aminoisobutyric acid transport, although it is necessary in this process. Cell survival was decreased both by photodynamic treatment and by hyperthermia. The combined effects of these two treatments were additive. It is discussed that these results indicate that photodynamic inhibition of 2-aminoisobutyric acid transport is not causally related to loss of clonogenicity, contrary to earlier suggestions.
Boegheim
J P
JP
Sylvius Laboratories, Department of Medical Biochemistry, Leiden, The Netherlands.
Lagerberg
J W
JW
Dubbleman
T M
TM
Van Steveninck
J
J
D000621:Aminoisobutyric Acids / Q000378:metabolism*; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D017324:Hematoporphyrin Derivative; D006415:Hematoporphyrins / Q000494:pharmacology*; D006358:Hot Temperature; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007700:Kinetics; D008027:Light; D051379:Mice; D014176:Protein Biosynthesis
D000621:Aminoisobutyric Acids; D006415:Hematoporphyrins; C100049:2-aminoisobutyric acid; D017324:Hematoporphyrin Derivative; D000841:Anisomycin; D006861:Hydrogen Peroxide