Cellular pharmacokinetics of doxorubicin in cultured mouse sarcoma cells originating from autochthonous tumors.
We have studied the cellular pharmacology of doxorubicin in a line of mouse sarcoma cells isolated from a dimethylbenzanthracene-induced autochthonous tumor. We have studied the cytotoxicity of the drugs as a function of the exposure dose and of the exposure time to the drug. Cytotoxicity was evaluated as the inhibition of the incorporation of [3H-methyl]-thymidine in the cellular nucleic acids. Intracellular drug concentrations were measured by spectrofluorometry. We have shown that the intracellular drug concentration was a linear function of the extracellular drug concentration up to 5 micrograms/ml; the cytotoxicity was an exponential function of the exposure dose up to 1 micrograms/ml, but it was not an exponential function of the exposure time: the cytotoxicity may therefore be very different for similar total drug exposures. Incubation with a low dose for a long time did not provide a cytotoxicity as high as that obtained with a high dose for a short period of time. These results emphasize the role of the peak concentration of doxorubicin for its maximal action in the target cell.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D013997:Time Factors
D003470:Culture Media; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D015127:9,10-Dimethyl-1,2-benzanthracene; D004317:Doxorubicin