Ground-based facilities for simulation of microgravity: organism-specific recommendations for their use, and recommended terminology.

Research in microgravity is indispensable to disclose the impact of gravity on biological processes and organisms. However, research in the near-Earth orbit is severely constrained by the limited number of flight opportunities. Ground-based simulators of microgravity are valuable tools for preparing spaceflight experiments, but they also facilitate stand-alone studies and thus provide additional and cost-efficient platforms for gravitational research. The various microgravity simulators that are frequently used by gravitational biologists are based on different physical principles. This comparative study gives an overview of the most frequently used microgravity simulators and demonstrates their individual capacities and limitations. The range of applicability of the various ground-based microgravity simulators for biological specimens was carefully evaluated by using organisms that have been studied extensively under the conditions of real microgravity in space. In addition, current heterogeneous terminology is discussed critically, and recommendations are given for appropriate selection of adequate simulators and consistent use of nomenclature.

Inhibition of aromatase activity by methyl sulfonyl PCB metabolites in primary culture of human mammary fibroblasts.

In this study, the effects on catalytic activity and mRNA levels of aromatase in primary human mammary fibroblasts were evaluated after exposure to promoter-specific modulators of aromatase expression and methyl sulfonyl polychlorinated biphenyl metabolites (MeSO(2)-PCBs). A method for fibroblast isolation from primary breast tissue was developed and optimized, and aromatase activity and promoter-specific mRNA levels were assessed in these cells after exposure to test compounds. A 24-h exposure of fibroblasts to dexamethasone (DEX) (1-100 nM) increased aromatase activity to a maximum of 313-fold. DEX also elevated promoter I.4-specific RNA levels. A 24-h exposure of fibroblasts to 3-MeSO(2)-PCB-132, 4-MeSO(2)-PCB-132, 4-MeSO(2)-PCB-91, or 4-MeSO(2)-PCB-149 (0.1-10 microM) resulted in a concentration-dependent decrease of aromatase activity. Exposure of fibroblasts to MeSO(2)-PCBs just for the limited duration (6 h) of the catalytic assay caused a concentration-dependent inhibition of aromatase enzyme activity. mRNA levels were not altered by a 24-h MeSO(2)-PCB exposure nor was cytotoxicity observed. In aromatase-expressing human adrenocortical carcinoma H295R cells, a 24-h exposure to 3-MeSO(2)-PCB-132, 4-MeSO(2)-PCB-132, 4-MeSO(2)-PCB-91, or 4-MeSO(2)-PCB-149 (0.1-10 microM) also resulted in a concentration-dependent decrease of aromatase activity. Additionally, there were no changes in aromatase mRNA levels after 24-h exposure of H295R cells to MeSO(2)-PCBs. We conclude that in primary human mammary fibroblasts as well as in H295R cells, aromatase inhibition by MeSO(2)-PCBs is likely to be due to catalytic inhibition.