Adriamycin uptake and metabolism in organotypic culture of A549 human adenocarcinoma cells according to the exposure time.
In organotypic cultures (nodules) of A 549 human lung adenocarcinoma cells, the long-term cytotoxicity of Adriamycin is strongly improved by shortening the exposure time to the drug. In order to gain insight into the mechanisms of Adriamycin toxicity in this system, we have examined the drug uptake, retention and metabolism by fluorescence microscopy and HPLC analysis. A 549 nodules efficiently metabolize Adriamycin, two major metabolites, adriamycinol and an aglycone derivative, as yet chemically unidentified, are formed and efficiently excreted. Kinetic data show that a long exposure to Adriamycin triggers its efflux from both the nucleus and the cytoplasm while stimulating its metabolism. Therefore, a long exposure time to the drug appears to trigger a process of cellular detoxification by favouring its excretion from the cells via increased metabolism.
Chevillard
S
S
Institut Curie, Section de Biologie, Paris, France.
Vielh
P
P
Bastian
G
G
Coppey
J
J
D000230:Adenocarcinoma / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D004317:Doxorubicin