rifampin and Carcinoma--Ehrlich-Tumor

The effect of an in vivo treatment with two commonly employed drugs that are P-glycoprotein substrates, verapamil and rifampicin, on Ehrlich ascites carcinoma cells, was evaluated. Ehrlich ascites carcinoma cells were inoculated i.p. in CD-1 mice and animals were orally treated for 10 days with rifampicin (60 mg/kg/day) or verapamil (6 mg/kg/day). In the harvested cells the transcripts for mdr1a and mrp1, but not those for mdr1b, mrp2 and CYP3A, were detected, and treatment with verapamil or rifampicin did not modify the levels of the transcripts. On the contrary, an increased expression of P-glycoprotein was observed at the protein level with Western blot. The intracellular uptake of doxorubicin, a P-glycoprotein and MRP substrate, was significantly lower in cells obtained from treated animals in comparison with cells obtained from controls; in addition, the uptake was increased by a pretreatment with verapamil. The survival time of control animals implanted with untreated cells was similar to that of animals inoculated with cells obtained from rifampicin treated animals, however, the antineoplastic effect of doxorubicin was significanly higher in control animals. A treatment with rifampicin or verapamil in Ehrlich ascites tumor confers resistance to the antineoplastic drug doxorubicin, probably through an increased expression of P-glycoprotein.

Topics: Animals; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Blotting, Western; Calcium Channel Blockers; Carcinoma, Ehrlich Tumor; Doxorubicin; Drug Resistance, Multiple; Enzyme Inhibitors; Female; Mice; Reverse Transcriptase Polymerase Chain Reaction; Rifampin; Verapamil

Cyclosporin A inhibits the uptake of cholate into isolated hepatocytes in a non-competitive manner (Ki = 3.6 microM). It protects liver cells against phalloidin injury by a mixed competitive/non-competitive inhibition of phalloidin uptake (Ki = 0.08 microM). Rifampicin, a well-known substrate of the bilirubin transporter is also incorporated in a decreased quantity in the presence of cyclosporin A (IC50 = 80 microM). A photolabile diaziridine derivative of cyclosporin A was used for the identification of binding sites. In comparison with the original cyclosporin A the photoaffinity label exhibits a 2-3-fold lower affinity to the cholate (and phalloidin) transporter in the liver cell membrane. In the dark the label inhibits the uptake of both cholate and of phalloidin reversibly; after treatment with ultraviolet light flashes the inhibition becomes irreversible. The degree of inhibition is concentration dependent. Our results suggest binding of cyclosporin A to protein components of the cholate (and phalloidin) transporter of liver cells without uptake by this system. The inhibition of cholate (and phalloidin) uptake by cyclosporin A is non-competitive and may be due to nonspecific hydrophobic binding to compounds of the cholate transporter.

Topics: Aminoisobutyric Acids; Animals; Biological Transport; Carcinoma, Ehrlich Tumor; Cholic Acid; Cholic Acids; Cyclosporins; Kinetics; Liver; Mice; Oligopeptides; Phalloidine; Rifampin

The cytotoxicity of 2 rifamycin derivatives, rifazone-82 and rifampicin, on mouse ascites cells was studied, using the [125I]iododeoxyuridine (IUDR) method of labeling the tumor cells. This technique allows a distinction to be made between a cytocidal and cytostatic effect. The 2 drugs exerted a cytocidal effect against 2 non-leukemic cell lines, but had no effect against 3 leukemic lines.

Topics: Adenocarcinoma; Animals; Carcinoma, Ehrlich Tumor; Cell Line; Cell Survival; Female; Idoxuridine; Iodine Radioisotopes; Leukemia, Experimental; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Rifampin; Rifamycins; Transplantation, Homologous

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cyanates; In Vitro Techniques; Leukemia L1210; Methylnitrosourea; Mice; Mice, Inbred Strains; Nitrosourea Compounds; Protein Biosynthesis; Rifampin; RNA, Neoplasm

Topics: Ammonium Sulfate; Animals; Carcinoma, Ehrlich Tumor; Cell Nucleus; Chemical Precipitation; Dactinomycin; DNA; DNA-Directed RNA Polymerases; Enzyme Activation; Magnesium; Manganese; Mice; Osmolar Concentration; Ribonucleotides; Rifampin; Rifamycins; RNA; Spermine; Templates, Genetic; Tritium; Ultracentrifugation; Vibration

Topics: Animals; Carcinoma, Ehrlich Tumor; Cell Fractionation; Chromatography, Ion Exchange; Dactinomycin; DNA-Directed RNA Polymerases; DNA, Mitochondrial; Female; Mice; Mice, Inbred Strains; Mitochondria; Mitochondria, Liver; Mycotoxins; Peptides; Rats; Rifampin

Topics: Animals; Carbon Radioisotopes; Carcinoma, Ehrlich Tumor; Cats; Chromatin; Chromatography, Gel; DNA; DNA-Directed RNA Polymerases; Isotope Labeling; Mice; Nucleic Acid Hybridization; Nucleoproteins; Organ Specificity; Osmolar Concentration; Rifampin; RNA, Messenger; Species Specificity; Templates, Genetic; Thymus Gland; Time Factors; Transcription, Genetic; Uracil Nucleotides

Topics: Animals; Carcinoma, Ehrlich Tumor; Depression, Chemical; DNA; Escherichia coli; Phosphorus Isotopes; Rifampin; RNA; RNA Nucleotidyltransferases; RNA, Bacterial; RNA, Neoplasm; Tritium