ABSTRACT
The ability of three benzodiazepine tranquilizers, diazepam, oxazepam and chlordiazepoxide chlorhydrate to block metabolic cooperation between human hepatoma cells was analysed using autoradiographical monitoring. Independent tests were performed with compound concentrations varying from 1 to 50 micrograms/ml. The results showed that at a toxic dose of 50 micrograms/ml diazepam and oxazepam markedly inhibited metabolic cooperation and that oxazepam remained effective at a lower, non-toxic, dose (10 micrograms/ml). Chlordiazepoxide chlorhydrate was found to be less toxic than diazepam and oxazepam and did not interfere with metabolic cooperation at any concentration up to 50 micrograms/ml.
Subject(s)
Anti-Anxiety Agents/toxicity , Cell Communication/drug effects , Benzodiazepines , Carcinoma, Hepatocellular/metabolism , Cell Line , Dose-Response Relationship, Drug , Humans , Liver Neoplasms/metabolismABSTRACT
Metabolic cooperation between cells from three human hepatoma cell lines was studied by the clonogenic method and by autoradiography. It was found that human HGPRT+/HGPRT- SK-HEP-1 cells only, showed a metabolic cooperation capacity that was inhibited by tumour promoters 12-O-tetradecanoylphorbol-13-acetate (TPA) and phenobarbital, and was not inhibited by the non-promoter 4-O-methyl TPA, provided suitable experimental conditions (short exposure times) were used. This biological system might be the basis of a new in vitro short-term screening test for potential tumour-promoting chemicals.
Subject(s)
Carcinogens/pharmacology , Carcinoma, Hepatocellular/metabolism , Cell Communication , Liver Neoplasms/metabolism , Carcinoma, Hepatocellular/ultrastructure , Cell Line , Humans , Hypoxanthine Phosphoribosyltransferase/analysis , Liver Neoplasms/ultrastructure , Phenobarbital/pharmacology , Tetradecanoylphorbol Acetate/analogs & derivatives , Tetradecanoylphorbol Acetate/pharmacologyABSTRACT
Five established hepatoma cell lines, 1 of rat origin and 4 derived from human liver carcinoma, were compared for their capacity to perform metabolic activation of one polycyclic hydrocarbon, benzo[a]pyrene (BP), and one cyclodiene chlorinated insecticide, aldrin. The results of these investigations indicated both species and individual differences among these cell lines. Aldrin was found to be converted into dieldrin much more efficiently by the rat hepatoma cell line than by any human cell lines, whereas 2 human lines displayed the highest BP-metabolizing activity whether measured as the amounts of water-soluble products or estimated by cytotoxic cell-mediated assays. Results also showed that one particular human cell line can replace, advantageously, V79 hamster cells as target in a cell-mediated assay owing to its incapability to metabolize BP and its high sensitivity to BP metabolites.
Subject(s)
Aldrin/metabolism , Benzopyrenes/metabolism , Carcinogens/metabolism , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms, Experimental/metabolism , Liver Neoplasms/metabolism , Animals , Benzo(a)pyrene , Biotransformation , Cell Line , Cell Survival/radiation effects , Cricetinae , Cricetulus , Cytotoxicity, Immunologic , Humans , Kinetics , Lung , Rats , Species SpecificityABSTRACT
3 hybrid cell lines between mouse fibroblasts (A9) and mouse lymphoma cells (L5178YS) were compared with regard to the ability of UV-pre-irradiated cells to replicate intact (unirradiated) Minute-virus-of-Mice (MVM) and to reactivate UV-irradiated MVM. UV irradiation of cells before virus infection enhanced their ability to plaque intact virus (Enhanced Capacity) to a similar extent in the 3 hybrid cell lines. However, pretreatment of cells with UV radiation enhanced the survival of UV-damaged virus (Enhanced Reactivation) in only 1 of these hybrids. The lack of detectable Enhanced Reactivation in the other hybrids without concomitant change in their Enhanced Capacity, suggests that these processes are at least partly independent. Virus survival in unirradiated cells was similar for all 3 hybrid cell lines, indicating that the absence of detectable Enhanced Reactivation in 2 of the hybrids was not due to the constitutive expression of this process, but might rather result from its loss or extinction. The expression of both Enhanced Capacity and Enhanced Reactivation requires synthesis of protein de novo shortly after cell irradiation.
Subject(s)
Hybrid Cells/radiation effects , Minute Virus of Mice/radiation effects , Parvoviridae/radiation effects , Virus Activation/radiation effects , Virus Replication/radiation effects , Animals , Humans , Mice , Time Factors , Ultraviolet Rays , Viral Plaque AssaySubject(s)
Caffeine/pharmacology , Hybrid Cells/radiation effects , Animals , Cell Line , Cell Survival/drug effects , Cell Survival/radiation effects , Chromosome Mapping , Dose-Response Relationship, Radiation , Fibroblasts , Hybrid Cells/drug effects , Leukemia L5178 , Mice , Ploidies , Ultraviolet RaysABSTRACT
Cultured skin fibroblasts derived from unrelated patients with diagnosed cystic fibrosis were compared with those from one normal individual in respect to thymidine and uridine uptake. The results obtained show that the two nucleosides are incorporated at the same rate by the three cell strains. Therefore, it appears that the reported abnormality [6] in nucleoside uptake in cystic fibrosis cells is not a general characteristic of these cells.
