The identification of potential mutagens focusses on electrophilic food contaminants such as the mycotoxin patulin and electrophilic biotransformation products of contaminants and endogenous compounds. The Lehmann lab has identified the mutagenic potential of the mycotoxins patulin and alternariol (Schumacher et al. 2005; 2006; Lehmann et al., 2006; Brugger et al., 2007) and of catecholic biotransformation products of the soy isoflavones daidzein (Lehmann et al., 2006) and of low chlorinated biphenyls (Zettner et al., 2007, Lehmann et al., 2007) and further characterized their mode of action. Catecholic biotransformation products of 17β-estradiol, isoflavones and low chlorinated biphenyls induced besides gene mutations also aneuploidy (Lehmann et al., 2005, Lehmann et al., 2006; Zettner et al., 2007). This mechanism, in which Dr. Lehmann is interested since her Ph.D. research (Lehmann and Metzler, 2004), will be investigated for those compounds in the future.
The mutagenic process induced by those compounds can be significantly modulated by other food constituents on the level of toxicokinetics both and of the sensitivity of the target cells towards DNA damage. An important role plays the activation of cellular signaling pathways controlling absorption, biotransformation capacity, proliferation, differentiation and cellular stress response. The Lehmann lab focusses on signaling pathways interacting with steroid hormone receptors and Wnt proteins.
The Lehmann lab identified the estrogenic activity of the mycotoxin alternariol and of oxidation products of 17β-estradiol, daidzein, and of the phytosterol stigmasterol for the first time (Lehmann et al., 2006a; 2006b; Newill et al., 2007). Next, the estrogen receptor-dependent shift of the biotransformatio of 17β-estradiol towards its potentially carcinogenic metabolite 4-hydroxyestradiol by the soy isoflavones genistein and daidzein was revealed using cultured human mammary adenocarcinoma cells (Lehmann et al., 2008). The impact of the modulation of biotransformation on the mutagenicity of 17β-Estradiol in vitro was investigated in a DFG-funded project (Le 1329/7-1). Based on the insight gained by this project, a project investigating the impact of dietary supplements containing soy isoflavones on the human and animal mammary gland (Le 1329/10-1) and the development of an ex vivo model of the human mammary gland are currently worked on.
In another line of investigations, the Lehmann lab demonstrated in the DFG-funded project Le 1329/8-1, that genistein and low-chlorinated biphenyls exhibiting a hydroquinone moiety influence the Wnt-signaling pathway in cultured endometrial adenocarcinom cells in the same way as the synthetic estrogen diethylstilbestrol (Wagner und Lehmann, 2006; Wagner und Lehmann, 2010), which is a known transplacental carcinogen of the female reproductive tract as well as of the female mammary gland. A follow-up project investigating gene expression profiles in specific cell types of the developing endometrium under the influence of genistein is currently in preparation.