TY - GEN A1 - Rutz, Lukas A1 - Gao, Lan A1 - Küpper, Jan-Heiner A1 - Schrenk, Dieter T1 - Structure-dependent genotoxic potencies of selected pyrrolizidine alkaloids in metabolically competent HepG2 cells T2 - Archives of Toxicology N2 - 1,2-unsaturated pyrrolizidine alkaloids (PAs) are natural plant constituents comprising more than 600 different structures. A major source of human exposure is thought to be cross-contamination of food, feed and phytomedicines with PA plants. In humans, laboratory and farm animals, certain PAs exert pronounced liver toxicity and can induce malignant liver tumors in rodents. Here, we investigated the cytotoxicity and genotoxicity of eleven PAs belonging to different structural classes. Although all PAs were negative in the fluctuation Ames test in Salmonella, they were cytotoxic and induced micronuclei in human HepG2 hepatoblastoma cells over-expressing human cytochrome P450 3A4. Lasiocarpine and cyclic diesters except monocrotaline were the most potent congeners both in cytotoxicity and micronucleus assays with concentrations below 3 μM inducing a doubling in micronuclei counts. Other open di-esters and all monoesters exhibited weaker or much weaker geno- and cytotoxicity. The findings were in agreement with recently suggested interim Relative Potency (iREP) factors with the exceptions of europine and monocrotaline. A more detailed micronuclei analysis at low concentrations of lasiocarpine, retrorsine or senecionine indicated that pronounced hypolinearity of the concentration–response curves was evident for retrorsine and senecionine but not for lasiocarpine. Our findings show that the genotoxic and cytotoxic potencies of PAs in a human hepatic cell line vary in a structure-dependent manner. Both the low potency of monoesters and the shape of prototype concentration–response relationships warrant a substance- and structure-specific approach in the risk assessment of PAs. KW - Genotoxicity KW - Liver cells KW - Micronuclei KW - Mutagenicity KW - Pyrrolizidine alkaloids KW - Relative potencies Y1 - 2020 UR - https://link.springer.com/article/10.1007/s00204-020-02895-z U6 - https://doi.org/10.1007/s00204-020-02895-z SN - 0340-5761 SN - 1432-0738 VL - 94 IS - 12 SP - 4159 EP - 4172 ER - TY - GEN A1 - Geburek, Ina A1 - Rutz, Lukas A1 - Gao, Lan A1 - Küpper, Jan-Heiner A1 - These, Anja A1 - Schrenk, Dieter T1 - The metabolic pattern of hepatotoxic pyrrolizidine alkaloids in liver cells T2 - Chemical Research in Toxicology N2 - Contamination with 1,2-unsaturated pyrrolizidine alkaloids (PAs) is a serious problem for certain phytomedicines, foods, and animal feeds. Several of these PAs are genotoxic and carcinogenic, primarily in the liver, upon cytochrome P450 (CYP)-catalyzed activation into reactive (pyrrolic and pyrrole-like) metabolites. Here we investigated the metabolism of selected PAs (echimidine, europine, lasiocarpine, lycopsamine, retrorsine, and senecionine) in rat hepatocytes in primary culture and in human CYP3A4-transfected HepG2 cells. The open-chained diesters echimidine and lasiocarpine and the cyclic diester senecionine were extensively metabolized in rat hepatocytes into a broad spectrum of products released into the medium. A large portion of unidentified, possibly irreversibly bound, products remained in the cells while detectable amounts of reactive and other metabolites were found in the incubation media. In HepG2-CYP3A4 cells, lasiocarpine was more extensively metabolized than echimidine and senecionine which also gave rise to the release of pyrrolic metabolites. In human cells, no pyrrolic metabolites were detected in retrorsine or lycopsamine incubations, while no such metabolites were detected from europine in both cell types. Other types of metabolic changes comprised modifications such as side chain demethylation or oxygenation reactions like the formation of N-oxides. The latter, considered as a detoxification step, was a major pathway with cyclic diesters, was less distinctive for echimidine and lycopsamine and almost negligible for lasiocarpine and europine. Our data are in agreement with previously published cyto- and genotoxicity findings and suggests that the metabolic pattern may contribute substantially to the specific toxic potency of a certain congener. In addition, marked differences were found for certain congeners between rat hepatocytes and transfected human HepG2 cells, whereby a high level of bioactivation was found for lasiocarpine, whereas a very low level of bioactivation was observed for monoesters, in particular in human cells. Y1 - 2021 UR - https://pubs.acs.org/doi/abs/10.1021/acs.chemrestox.0c00507 U6 - https://doi.org/10.1021/acs.chemrestox.0c00507 VL - 34 IS - 4 SP - 1101 EP - 1113 ER - TY - GEN A1 - Li, Bai A1 - Gao, Jiarong A1 - Wang, Xiuru A1 - Ma, Lan A1 - Cui, Qiang A1 - Veste, Maik T1 - Effects of biological soil crusts on water infiltration and evaporation Yanchi Ningxia, Maowusu Desert, China T2 - International Journal of Sediment Research N2 - Biological soil crusts serve as a vanguard for improving the ecological environment in arid, semi-arid desertification areas.It is a good indicator of the level of improvement which the local ecological evironment is undertaking. In desert areas, water condition is a key factor of improving the ecological environment. As a first layer protection, biological crusts play an important role in local vegetation succession due to their abilities to conserve and maintain moisture. Using Maowusu desert in Yanchi of Ningxia province as an example, after three years of research, this paper chooses three kinds of biological crusts including lichen, moss and cyanobacterial which are under the cover of Artemisia ordosicaas research objects. The results of this study indicate that, the closer biological crusts are to Artemisia ordosica vegetation, the thicker they become. In the same position of Artemisia ordosica vegetation, the thickness of moss crusts is the highest, followed by lichen crusts, and the thickness of cyanobacterial crusts is the lowest. Biological soil crusts coverage protects the natural water content of soil layers from 0 to 5cm. Also, it effects falling water to infiltrate deeper, and cannot prevent the surfacewater content from evaporating effectively. The effect of biological crusts blocking water infiltration decreases with the increase of rainfall. At the same rainfall level, moss crusts provide the strongest water infiltration blockage, followed by lichen crusts and cyanobacterial crusts. With the increase of rainfall, the depth of water infiltration increases.At the same rainfall level, the relationship of water infiltration depth is as follows: cyanobacterial crusts > lichen crusts > moss crusts. With the increase of biological crusts thickness, they blocking water infiltration capacity is stronger, and the depth of water infiltration is smaller. Analysis on the characteristic of simulated rainfall process on biological crusts shows that sandy land can be fixed by applying appropriate artificial biological crusts to build a sustainable forest protection system and to create a stable ecosystem in desertification area. Y1 - 2016 U6 - https://doi.org/10.1016/j.ijsrc.2016.05.005 SN - 1001-6279 VL - 31 IS - 4 SP - 311 EP - 323 ER -