Description: Das Projekt "Anwendung der besten verfuegbaren Verfahren zur Erkennung vermuteter Krebsausloeser beim Menschen" wird vom Umweltbundesamt gefördert und von Deutsches Krebsforschungszentrum - Stiftung des öffentlichen Rechts durchgeführt. In the first part of the study two tasks will be undertaken. First, the hierarchical relationship between DNA damage induced in rodents (comet assay) and mutation induction (lacZ mice) will be consolidated using recently defined tissue-specific genotoxic carcinogens. These carcinogens will be selected to focus the experimental evaluations in rodents on those tissues most often associated with chemically induced carcinogenesis in humans (respiratory tract, skin, gladder):. In parallel with these studies, environmental chemicals relevant to the EU will be prioritized by chemical structure, known genetic toxicity and estimated levels of human exposure. This will yield a priority list of 15 chemicals. The first associated partner will contribute to the process of prioritization over the first two years of the study using existing chemical lists/audits. These priority chemicals will be evaluated in rodents using the comet assay to define their primary targets of DNA reactivity. The nine most genotoxic of these compounds will be assessed for mutagenicity to lacZ transgenic mice. Restriction site mutagenesis within the target lacZ gene will also be studied in key affected tissues. Based on these data, a final group of six chemicals will be bioassayed for carcinogenicity over a period of six month using hemizygous P53 mice. P53 genes derived from selected tumours will be sequenced to determine the origin of their loss of function. Independent of these analyses, all bioassay tissues will be considered for possible future use. If the study succeeds in its aims, six presumptive human carcinogens will be identified for confirmation in subsequent human studies. Should the study fail, a re-appraisal of current approaches to the prediction of possible human carcinogens will be required.
Types:
SupportProgram
Origin: /Bund/UBA/UFORDAT
Tags: Gen ? Nagetier ? Kanzerogenität ? Mutation ? DNA ? Karzinogenese ? Mutagenität ? Schadstoffwirkung ? Atemtrakt ? Genotoxizität ? Kanzerogenitätsprüfung ? Maus ? Öffentliches Recht ? Umweltchemikalien ? Karzinogen ? Biotest ? Chemikalien ? Daten ? Haut ? Mensch ? Studie ? Toxizität ? Tumor ? Chemischer Altstoff ?
Region: Baden-Württemberg
Bounding box: 9° .. 9° x 48.5° .. 48.5°
License: cc-by-nc-nd/4.0
Language: Deutsch
Time ranges: 1996-05-01 - 1999-04-30
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