The tenth anniversary of the Björn Ekwall memorial foundation.

The Björn Ekwall Memorial Foundation (BEMF) was initiated by the Scandinavian Society for Cell Toxicology in 2001, to honour the memory of Dr Björn Ekwall (1940-2000) and to establish a prize, the Björn Ekwall Memorial Award. The prize is awarded to scientists who have significantly contributed to the field of cell toxicology, and whose work is contributing toward the replacement of animal experiments by alternative toxicity tests. Over the past 10 years, the Björn Ekwall Memorial Award has been presented annually.

Björn Ekwall, an outstanding Swedish cell toxicologist.

Dr. Björn Ekwall (1940-2000) was an outstanding Swedish cell toxicologist who made pioneering contributions to the field of in vitro toxicology. In particular, he formulated the so called "basal cytotoxicity concept" (1983) which provided a conceptual basis for the estimation of acute systemic toxicity of chemicals in humans by the use of in vitro tests.

Estimation of human blood LC50 values for use in modeling of in vitro-in vivo data of the ACuteTox project.

The main aim of the ACuteTox project, under EU 6th Framework programme, is to investigate whether animal toxicity tests for acute systemic toxicity could be replaced by a combination of alternative assays. Data for 97 reference chemicals was collected in the ACuteTox database (Acutoxbase), designed to handle invitro and invivo (human and animal) lodged data. The principal basis for demonstration of the applicability of invitro tests is the invitro-invivo modeling, by using statistical correlation between invitro IC50 molar values (the 50% inhibitory concentration for the endpoints measured) and human blood molar concentrations LC50 (50% lethal concentrations).

The integrated acute systemic toxicity project (ACuteTox) for the optimisation and validation of alternative in vitro tests.

The ACuteTox project is designed to replace animal testing for acute systemic toxicity, as is widely used today for regulatory purposes, by using in vitro and in silico alternatives. In spite of the fact that earlier studies on acute systemic toxicity demonstrated a good correlation between in vitro basal cytotoxicity data (the 50% inhibitory concentration [IC50]) in human cell lines and rodent LD50 values, and an even better correlation between IC50 values and human lethal blood concentrations, very few non-animal tests have been accepted for general use. Therefore, the aim of the ACuteTox project is to adapt new testing strategies, for example, the implementation of new endpoints and new cell systems for toxicity screening, organ-specific models, metabolism-dependent toxicity, tissue absorption, distribution and excretion, and computer-based prediction models.

Activity of epothilones.

Epothilones represent a novel class of anticancer drugs which inhibit the cell cycle and strongly influence cell division. The biological activity of epothilones is associated with their capacity to bind to the protein tubulin of microtubules and to disturb the dynamic equilibrium between microtubule assembling and disassembling. Consequently, in dividing cells, it leads to mitotic arrest and to apoptotic cell death.

INVITOX 2004: 13th Workshop of the European Society of Toxicology In Vitro, organised in cooperation with the Scandinavian Society for Cell Toxicology.

INVITOX 2004, the 13th Workshop of the European Society of Toxicology In Vitro, was held on 8-11 September 2004, in Zegrze, Poland, in cooperation with the Scandinavian Society for Cell Toxicology. The workshop was attended by 112 participants from 19 countries. The programme included 11 main sessions and two round table discussions.

BMS-310705 Bristol-Myers Squibb/GBF.

Bristol-Myers Squibb, in collaboration with the German Research Centre for Biotechnology, is developing BMS-310705, an epothilone analog, for the potential treatment of cancer. By April 2002, phase I trials of BMS-310705 were underway.

Use of the PFGE assay for studies of DNA breakage induced by toxic chemicals.

The relevance of the pulsed field gel electrophoresis (PFGE) assay for the estimation of the DNA damaging effects of chemicals was studied. Four chemicals were randomly chosen from the list of 50 Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) reference chemicals with known human acute systemic toxicity: acetylsalicylic acid, paracetamol, ethylene glycol and sodium chloride. Human fibroblasts (VH-10) were used as a model system.

New achievements in human cell toxicology: the 20th annual workshop on in vitro toxicology.

The 20th Annual Workshop on In Vitro Toxicology (Oxford, UK, September 22-24, 2002) was convened as part of a European meeting entitled Human Cell Culture 2002. The meeting was arranged by the Scandinavian Society for Cell Toxicology (SSCT), the European Tissue Culture Society and the British Prostate Group. Two sessions, which are summarised in this report, were devoted to in vitro toxicology: Human Cell Toxicology and The SSCT Free Paper Session.

Epothilone D (Kosan/Roche).

Kosan and Roche are developing the microtubule inhibitor epothilone D (KOS-862 and NSC-703147), an analog of epothilone B for the potential treatment of cancer. Phase II trials in colorectal, metastatic breast and non-small-cell lung cancers were initiated in December 2003.

Efaproxiral (Allos Therapeutics).

Allos Therapeutics Inc is developing the hemoglobin allosteric modifier efaproxiral as a potential radiosensitizer and chemotherapy enhancer in cancer therapy.

The Escherichia coli RecA protein complements recombination defective phenotype of the Saccharomyces cerevisiae rad52 mutant cells.

The Saccharomyces cerevisiae rad52 mutants are sensitive to many DNA damaging agents, mainly to those that induce DNA double-strand breaks (DSBs). In the yeast, DSBs are repaired primarily by homologous recombination (HR). Since almost all HR events are significantly reduced in the rad52 mutant cells, the Rad52 protein is believed to be a key component of HR in S.

Genotoxic effects of ethylene oxide, propylene oxide and epichlorohydrin in humans: update review (1990-2001).

Ethylene oxide (EtO), propylene oxide (PO) and epichlorohydrin (ECH) are important industrial chemicals widely used as intermediates for various synthetic products. EtO and PO are also environmental pollutants. In this review we summarize data published during the period 1990-2001 concerning both the genotoxic and carcinogenic effects of these epoxides in humans.

Development of an in vitro test battery for the estimation of acute human systemic toxicity: An outline of the EDIT project. Evaluation-guided Development of New In Vitro Test Batteries.

The aim of the Evaluation-guided Development of new In Vitro Test Batteries (EDIT) multicentre programme is to establish and validate in vitro tests relevant to toxicokinetics and for organ-specific toxicity, to be incorporated into optimal test batteries for the estimation of human acute systemic toxicity. The scientific basis of EDIT is the good prediction of human acute toxicity obtained with three human cell line tests (R(2) = 0.77), in the Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) programme.

Aphidicolin induces 6-thioguanine resistant mutants in human diploid fibroblasts.

Cytotoxic and mutagenic effects of aphidicolin (APC), an inhibitor of DNA polymerases alpha and delta, were studied in human diploid VH-10 fibroblasts. The cells were treated (2 or 4h) with APC at concentration ranges of 10-40 microM. The effect of APC on cell survival after 4 h treatment was significantly higher than after 2 h treatment.