Fluorine-19 NMR spectrometry was used to monitor the metabolism of two antineoplastic fluoropyrimidines, 5-fluorouracil (5FU) and 5'-deoxy-5-fluorouridine (5'dFUrd), in cell cultures of human pancreatic (Capan-1) and colon (HT-29) adenocarcinoma. The preliminary results showed, for the two tumor cell lines treated with 5FU, the presence in nonperfused cells of three signals corresponding to intracellular metabolites: 5FU, F-nucleotides and F-nucleosides. When the cells were perfused only the signals of F-nucleotides and 5FU were present. The F-nucleosides observed during the analysis of the nonperfused cells came from the conversion of F-nucleotides. During the NMR recording of Capan-1 cells at 37 degrees C the first metabolite of the catabolic pathway of 5FU, 5,6-dihydro-5-fluorouracil, occurred. At the beginning of the NMR recording of Capan-1 cells treated with 5'dFUrd, two signals corresponding to F-nucleotides and F-nucleosides (consistent with 5'dFUrd) were observed; during the analysis, a supplementary signal corresponding to 5FU appeared. Even after pretreatment with methotrexate the signal of 5FU incorporated into RNA was not detected. Our experiments, performed in attempts to observe the signal of the ternary complex between thymidylate synthetase (TS), 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) and 5,10-methylene-tetrahydrofolate (5,10-CH2FH4), allowed detection in some cases of a broad signal, whose chemical shift was similar to that reported in the literature following incubation of TS with FdUMP and 5,10-CH2FH4, but our results were not always reproducible.
The influence of pH variations on transplacental transfer of antipyrine was
studied using a human placental cotyledon perfused ex vivo. The antipyrine transfer rate is
positively correlated with the pH in the fetal circulation and negatively correlated with the
pH in the maternal circulation. Thus, the transfer rate is negatively correlated with the
difference between pH values in maternal and fetal circulations. The antipyrine transfer rate
is also positively correlated with the flows in maternal and fetal circulations. The above
parameters allowed to explain 50% of the variance on the transfer rates obtained in various
experimental conditions. In a final series of experiments where these parameters for each
placenta were fixed at identical values, a good reproducibility in the results was obtained, the
variation coefficient being 17%. Thus, establishing the effect of variations in pH allowed a
good standardization of the perfused cotyledon model. This effect cannot be explained by
modifications in the ionized fraction of the antipyrine molecule and is probably due to
physiological mechanisms.
Empirical factors for converting 3 H thymidine incorporation into bacterial production were determined from samples laken in a mesotrophic lake. Twenty five diluted water cultures were conducted at « in situ » temperature (4-22° C) from April 1987 to February 1989. The conversion factors varied through the year ; the average conversion factor was 6.29 x I0 9 cells (2-10.7) per nanomole of thymidine incorporated into cold TCA precipitate and 7.18 x 10 9 cells (3.47-10.7) nmoM, when corrected for the increase in cell biomass which occured during the incubations. The validity of these factors, higher than the theoretical conversion factors values, is discussed considering the diluted water culture conditions and the data analysis methods. Validité des facteurs utilisés pour convertir l'incorporation de thymidine tritiée en production bactérienne. Mots clés : Eau douce, production bactérienne, thymidine, facteurs de conversion. Les facteurs de conversion permettant d'estimer la production bactérienne à partir de l'incorporation de 3 H thymidine ont été déterminés de façon empirique à partir d'échantillons d'eau prélevés dans un lac mésotrophe. Vingt-cinq cultures en eau diluée ont été faites à température « in situ » entre avril 1987 et Février 1989. Les facteurs de conversion varient au cours de l'année ; ils sont en moyenne de 6,29 x 10 9 cellules (2-10,7) par nanomole de thymidine incorporée dans la fraction TCA insoluble et de 7,18 x I0 9 cellules (3,47-10,7) nmol-1 , si l'on tient compte de l'accroissement de taille des cellules. La validité de ces facteurs, supérieurs aux facteurs de conversion théoriques, est discutée en fonction des conditions de culture et du mode d'analyse des données.
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