Relationship between photodynamically induced damage to various cellular parameters and loss of clonogenicity in different cell types with hematoporphyrin derivative as sensitizer.
The possible causal relationship between various forms of photodynamically inflicted damage and reproductive cell death of cultivated cells was evaluated according to three criteria. The probability for the existence of such a relationship is high, when the particular form of cellular damage (i) exhibits a dose-effect curve, comparable to the dose-effect curve of loss of clonogenicity, (ii) is not readily repairable during further incubation of the treated cells and (iii) varies in a way comparable to the loss of clonogenicity under varying experimental conditions. According to these criteria it could be shown that many forms of photodynamically inflicted cellular damage are presumably not directly involved in loss of clonogenicity. Only for a few kinds of cellular damage studied in the present investigations was the probability for a causal relationship with reproductive cell death much higher. For L929 fibroblasts this is either an inhibition of the Na+/K(+)-ATPase activity, or a relatively slight DNA damage combined with a strong inhibition of DNA excision repair. For T24 human bladder carcinoma cells the kinds of cellular damage that may be causally related to reproductive cell death are again inhibition of Na+/K(+)-ATPase activity, inhibition of amino-acid (AIB and glycine) transport activity or impairment of mitochondrial function. Finally, for CHO cells, inhibition of leucine and phenylalanine transport and impairment of mitochondrial function may be crucial for loss of clonogenicity. These results indicate that the pathways leading to photodynamically induced reproductive cell death may be quite different for different cell types.
Penning
L C
LC
Department of Medical Biochemistry, Sylvius Laboratory, Leiden, The Netherlands.
Tijssen
K
K
Boegheim
J P
JP
van Steveninck
J
J
Dubbelman
T M
TM
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000528:radiation effects; D016466:CHO Cells; D016923:Cell Death; D002455:Cell Division; D002462:Cell Membrane / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D006415:Hematoporphyrins / Q000494:pharmacology*; D006801:Humans; D007739:L Cells; D007930:Leucine / Q000378:metabolism; D051379:Mice; D010777:Photochemistry; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000528:radiation effects; D014443:Tyrosine / Q000378:metabolism
D006415:Hematoporphyrins; D014443:Tyrosine; D000254:Sodium-Potassium-Exchanging ATPase; D007930:Leucine