Biomedical subjects

B Hietel

Publications and source records attributed to B Hietel.

8 recordsLinked to original sources

PubMed1994

Cisplatin resistance in mouse fibrosarcoma cells after low-dose irradiation in vitro and in vivo.

Murine fibrosarcoma cells (SSK) exhibit a transient cisplatin resistance after low-dose irradiation (5 x 2 Gy) in vitro and in vivo. When resistance is lost, it can be restored by a single drug exposure which, without preirradiation, does not generate cisplatin resistance in parental cells. There is no cross-resistance to radiation. Metallothioneins, which are associated with cisplatin resistance after high-dose irradiation (15 x 6 Gy), do not correlate with induction and loss of cisplatin resistance after low-dose irradiation. Since cisplatin survival curves are also monotonous when drug resistance diminishes, an adaptive response is more likely than a mutational event to underlie cisplatin-induced resistance. Drug resistance can be overcome by combined exposure to cisplatin in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Under these conditions, cisplatin sensitivity is increased 2.4- to 2.8-fold in the resistant strains compared with only 1.5- to 1.8-fold in the parental cells. The cellular platinum content with and without IBMX treatment is not significantly different in sensitive and resistant cells. Loss of drug resistance correlates with a decrease in cisplatin sensitisation by IBMX. This suggests that cisplatin resistance after low-dose irradiation may be associated with alterations of the cAMP-dependent signal transduction pathway.

1-Methyl-3-isobutylxanthine↗

PubMed1993

Transient cisplatin-resistant murine fibrosarcoma cell characterized by increased metallothionein content.

Cisplatin-resistant mouse fibrosarcoma cells, SSK-R, were isolated after short and low-dose drug treatment of the sensitive SSK cells in vitro. These SSK-R sublines exhibit up to sevenfold cisplatin resistance and are characterized mainly by an increased metallothionein content. Loss of drug resistance after about 140-180 cell divisions in drug-free medium coincides with loss of metallothionein content. The glutathione level is the same in the sensitive and resistant sublines; inhibition of glutathione synthesis by buthionine sulphoximine enhances the sensitivity in both cells lines by a factor of 2.7. The resistant sublines are not cross-resistant to radiation; a radiation exposure followed immediately by cisplatin treatment results in an additive effect. The cellular cisplatin content is slightly reduced in SSK-R2 cells and it remains at this level also upon loss of drug sensitivity.

Animals↗

PubMed1993

Radiation-induced transient cisplatin resistance in murine fibrosarcoma cells associated with elevated metallothionein content.

Cisplatin resistant mouse fibrosarcoma cells were isolated after fractionated irradiation in the absence of any drug treatment. Several sublines have been established; clone SSK-rad1 was used for further studies. These cells exhibit unchanged radiosensitivity and are compared to cisplatin resistant sublines, SSK-cis2, previously induced by low dose cisplatin exposure. Both resistant sublines are characterised by reduced CdCl2 sensitivity, indicating enhanced metallothionein content; loss of cisplatin resistance occurs after 10 to 25 generations and correlates with rising CdCl2 toxicity. Increase of MT is demonstrated directly by 109Cd binding to the MT containing region after FPLC. Both sublines differ in GSH level, which is increased only in SSK-rad1 cells, and in cellular platinum content, which is reduced in SSK-cis2 cells compared to the parental SSK cell line. These factors may contribute to cisplatin resistance but are not the main cause responsible for the transient nature of the drug resistance observed. Our results indicate that transient cisplatin resistance in SSK cells can be induced not only by the drug itself but also by gamma-irradiation and is based on the same mechanism of increased cellular MT content.

Animals↗

PubMed1989

Radiation inactivation analysis of the A1 adenosine receptor of rat brain. Decrease in radiation inactivation size in the presence of guanine nucleotide.

Radiation inactivation analysis of the binding of the A1 adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine to rat brain membranes yielded a radiation inactivation size of 58 kDa. In the presence of GTP gamma S this was reduced to 33 kDa, in good agreement with the size of the ligand-binding subunit detected after photoaffinity labelling. The data indicate that the structural association of A1 adenosine receptors with G-protein components is altered in situ in the presence of guanine nucleotides.

Adenosine↗

PubMed1986

Target size analysis of opioid receptors. No difference between receptor types, but discrimination between two receptor states.

Target size analysis of opioid receptor is complicated by the presence of multi-exponential inactivation curves. Irradiation of intact frozen tissue proved essential to eliminate such artifacts, due to indirect irradiation effects. Upon irradiation condition, opioid binding activity was inactivated in a single mono-exponential manner. Identical inactivation curves were obtained for mu, delta and kappa binding activities in brain membranes from rat, guinea-pig and frog and in NG 108-15 cells: the molecular mass obtained was 98 +/- 2 kDa. However, when opioid binding was assayed in the presence of Na+, Mg2+ and GTP, the molecular mass was found to be only 56 +/- 4.4 kDa. We suggest that the opioid recognition site comprises a unit of 56 kDa and that in the absence of Na+, Mg2+ and GTP an additional membrane component of 40-44 kDa is necessary for high-affinity opioid binding.

Animals↗

PubMed1986

The relationship between cisplatin sensitivity and drug uptake into mammalian cells in vitro.

Clonogenic survival of HeLa, Chinese hamster and HaK cells after treatment with a range of cisplatin concentrations and exposure times was determined and cellular platinum concentrations were measured by PIXE. It was demonstrated that cisplatin cytotoxicity of the three cell lines varied considerably as a function of drug exposure dose. These differences are related to differential cellular drug uptake.

Animals↗

PubMed1983

The molecular size of multiple opiate receptors.

The functional size of different types of opiate receptors was determined in situ by the radiation inactivation technique. The Mr of opiate binding sites was estimated to be about 90,000 daltons; the data revealed no significant differences between the molecular sizes of either mu-, delta- or kappa-sites in rat brain membranes. An identical molecular size was found also for the delta-sites in the neuroblastoma X glioma hybrid cell clone, NG 108-15.

Animals↗

PubMedDate not supplied

Heat sensitization to cisplatin in two cell lines with different drug sensitivities.

Heat sensitization to cisplatin was studied in drug-sensitive Chinese hamster fibroblast (CH) and inherently drug-resistant hamster kidney (HaK) cells. Under normothermic conditions the slopes of the survival curves differed by a factor of 3.6, while the cellular uptake was higher in CH cells by a factor of 3. When heat and drug treatment were given simultaneously, both effects were increased in CH and HaK cells: thermal enhancement factors at 43 degrees C were 5.5 (CH) and 2.9 (HaK) for cytotoxic drug action and 3.9 and 2.2 for the increase in cellular drug content. Increase in cell sensitization was also obtained if the cells were heat pretreated (42.5-44 degrees C for various times) followed by drug exposure at 37 degrees C. It is concluded that thermal enhancement depends on the efficiency of cisplatin cytotoxicity, which in turn correlates with cellular drug uptake in both the sensitive and resistant cell line.

Animals↗