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In the EU, there are no specific legal regulations regarding microbial food cultures. However, at European and national level, there are regulations that require microbial cultures to be checked in terms of their compliance with legal requirements. Due to the lack of definitions for microbial food cultures with various applications, there are uncertainties regarding how they are to be assessed. The increased elaboration of microbial ecology and modern taxonomy has allowed the description of numerous new species that are attractive for use in food cultures or are already in use, on which, however, only limited experience is available. In view of these developments, the SKLM has prepared this statement, focusing on definitions, gaps in knowledge and further research needs. It aims to support the producers and users of microbial cultures as well as authorities responsible for consumer health protection with respect to safety assessment and to contribute to consumer information. The scientific status concerning these cultures in food technology, the traditional roots of their application and their potential for sustaining and/or furthering food variety and quality have not been adequately described up to now. This is the subject of the present SKLM statement. In addition, definitions are proposed for cultures used in food technology that may also be useful for the assessment in a legal context. The opinion was released in German on 29 March 2010, the English version was agreed on 15 November 2010., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The Senate Commission on Food Safety (SKLM, Senatskommission zur gesundheitlichen Bewertung von Lebensmitteln) of the German Research Foundation (DFG, Deutschen Forschungsgemeinschaft) is a transdisciplinary expert committee, providing advice on food safety to the government, parliament, and authorities. Consultation is based on a scientific assessment with the aim to give expert advice to authorities, so that they can make appropriate decisions. The SKLM is independent in its scientific deliberations and under no directive in the selection of issues to work on. Topics considered may result from requests of the Federal Ministry of Food, Agriculture, and Consumer Protection (BMELV, Bundesministeriums für Ernährung, Landwirtschaft und Verbraucherschutz). Other issues may be raised by the SKLM, if they are regarded to be of particular importance for consumer health protection. Issues encompass the scientific assessment of safety and nutritional benefit of food ingredients and additives, of novel and functional food, as well as of novel food technologies. The SKLM identifies gaps in knowledge, research needs, and need for action.

Tyrosyl DNA phosphodiesterase 1 (TDP1) is a repair enzyme that removes adducts, e.g. of topoisomerase I from the 3'-phosphate of DNA breaks. When expressed in human cells as biofluorescent chimera, TDP1 appeared more mobile than topoisomerase I, less accumulated in nucleoli, and not chromosome-bound at early mitosis. Upon exposure to camptothecin both proteins were cleared from nucleoli and rendered less mobile in the nucleoplasm. However, with TDP1 this happened much more slowly reflecting most likely the redistribution of nucleolar structures upon inhibition of rDNA transcription. Thus, a steady association of TDP1 with topoisomerase I seems unlikely, whereas its integration into repair complexes assembled subsequently to the stabilization of DNA.topoisomerase I intermediates is supported. Cells expressing GFP-tagged TDP1 > 100-fold in excess of endogenous TDP1 exhibited a significant reduction of DNA damage induced by the topoisomerase I poison camptothecin and could be selected by that drug. Surprisingly, DNA damage induced by the topoisomerase II poison VP-16 was also diminished to a similar extent, whereas DNA damage independent of topoisomerase I or II was not affected. Overexpression of the inactive mutant GFP-TDP1(H263A) at similar levels did not reduce DNA damage by camptothecin or VP-16. These observations confirm a requirement of active TDP1 for the repair of topoisomerase I-mediated DNA damage. Our data also suggest a role of TDP1 in the repair of DNA damage mediated by topoisomerase II, which is less clear. Since overexpression of TDP1 did not compromise cell proliferation, it could be a pleiotropic resistance mechanism in cancer therapy.

The cAMP-specific phosphodiesterase isoenzyme family PDE4 represents the highest cAMP-hydrolysing activity in many human cancer cell lines including the human large cell lung carcinoma cell line LXFL529L. Treatment of LXFL529L cells with the potent PDE4 inhibitor 7-benzylamino-6-chloro-2-piperazino-4-pyrrolidino-pteridine (DC-TA-46) induces dose-dependent growth inhibition. Cells are arrested in the G(1)-phase of the cell cycle and the induction of apoptosis is observed. In this study, we investigated the effect of DC-TA-46 on downstream elements of the cAMP-pathway. DC-TA-46 mediated inhibition of PDE4 activity in LXFL529L cells resulted in an increase of the intracellular cAMP level and significant induction of the activity of protein kinase A (PKA). The regulatory PKA subunit RIalpha was predominantly expressed in LXFL529L cells. In contrast to effects induced by cAMP analogues like 8-Cl-cAMP, the expression of the regulatory subunits of PKA remained unaffected by DC-TA-46. Treatment of LXFL529L cells with DC-TA-46 enhanced the binding of nuclear proteins to the cAMP-responsive element (CRE) consensus sequence TGACGTCA in a time- and dose-dependent manner, indicating the activation of transcription factors by PKA phosphorylation.