RESUMEN
The overexpression of human cytochrome P450 CYP1B1 has been observed in a wide variety of malignant tumours, but the protein is undetectable in normal tissues. A number of cytochrome P450 enzymes are known to metabolise a variety of anticancer drugs, and the consequence of cytochrome P450 metabolism is usually detoxification of the drug, although bioactivation occurs in some cases. In this study, a Chinese hamster ovary cell line expressing human cytochrome P450 CYP1B1 was used to evaluate the cytotoxic profile of several anticancer drugs (docetaxel, paclitaxel, cyclophosphamide, doxorubicin, 5-fluorouracil, cisplatin, and carboplatin) commonly used clinically in the treatment of cancer. The MTT (3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide) assay was used to determine the levels of cytotoxicity. The key finding of this study was that on exposure to docetaxel, a significant decrease in sensitivity towards the cytotoxic effects of docetaxel was observed in the cell line expressing CYP1B1 compared to the parental cell line (P = 0.03). Moreover, this difference in cytotoxicity was reversed by co-incubation of the cells with both docetaxel and the cytochrome P450 CYP1 inhibitor alpha-naphthoflavone. This study is the first to indicate that the presence of CYP1B1 in cells decreases their sensitivity to the cytotoxic effects of a specific anticancer drug.
Asunto(s)
Antineoplásicos/farmacología , Hidrocarburo de Aril Hidroxilasas , Sistema Enzimático del Citocromo P-450/metabolismo , Resistencia a Antineoplásicos/fisiología , Paclitaxel/análogos & derivados , Taxoides , Animales , Antineoplásicos/metabolismo , Células CHO , Supervivencia Celular/efectos de los fármacos , Cricetinae , Citocromo P-450 CYP1B1 , Sistema Enzimático del Citocromo P-450/genética , Docetaxel , Humanos , Paclitaxel/metabolismo , Paclitaxel/farmacología , TransfecciónAsunto(s)
Hidrocarburo de Aril Hidroxilasas , Sistema Enzimático del Citocromo P-450/biosíntesis , Hígado/enzimología , Oxidorreductasas N-Desmetilantes/biosíntesis , Animales , Sangre , Bovinos , Células Cultivadas , Medios de Cultivo , Citocromo P-450 CYP3A , Dexametasona/farmacología , Perros , Inducción Enzimática/efectos de los fármacos , Femenino , Feto , Humanos , Hígado/citología , Ratas , Ratas Sprague-Dawley , Rifampin/farmacologíaRESUMEN
Directional ocean wave spectra derived from Shuttle Imaging Radar-B (SIR-B) L-band imagery collected off the coast of southern Chile on 11 and 12 October 1984 were compared with independent spectral estimates from two airborne scanning radars. In sea states with significant wave heights ranging from 3 to 5 meters, the SIR-B-derived spectra at 18 degrees and 25 degrees off nadir yielded reasonable estimates of wavelengths, directions, and spectral shapes for all wave systems encountered, including a purely azimuth-traveling system. A SIR-B image intensity variance spectrum containing predominantly range-traveling waves closely resembles an independent aircraft estimate of the slope variance spectrum. The prediction of a U.S. Navy global spectral ocean wave model on 11 October 1984 exhibited no significant bias in dominant wave number but contained a directional bias of about 30 degrees espect to the mean of the aircraft and spacecraft estimates.