Cytotoxic effects and pharmacokinetic analysis of combined adriamycin and X-ray treatments in human organotypic cell cultures.
Organotypic cultures of human A549 cells were used as a tumor model to investigate sequence effects for combination treatments with adriamycin (ADR) and X-irradiation. Initial drug exposure led to the greatest cytotoxic effect especially when X-rays were delivered 24 h later and this subsequent irradiation did not significantly modify the intracellular ADR concentration. In contrast, post-irradiation drug exposure gave rise to a lower cytotoxic effect, and induced a marked reduction of intracellular and more specifically intranuclear ADR uptake and retention, especially when the drug was given 24 h later.
Chevillard
S
S
Section de Biologie, Institut Curie, Paris, France.
Vielh
P
P
Campana
F
F
Bastian
G
G
Coppey
J
J
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002467:Cell Nucleus / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D011878:Radiotherapy; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D004317:Doxorubicin