@article{EpeHarttigStopperetal.1990,
  author    = {Epe, B. and Harttig, U. and Stopper, Helga and Metzler, M.},
  title     = {Covalent binding of reactive estrogen metabolites to microtubular protein as a possible mechanism of aneuploidy induction and neoplastic cell transformation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63478},
  year      = {1990},
  abstract  = {Neoplastic cell transfonnation induced by estrogens and some other carcinogen\& such as benzene appears to involve the induction of mitotic aneuploidy rather than DNA damage and point mutations. As metabolic activation may also play an important roJe in the mechanism of carcinogenesis of these nongenotoxic compounds, we have studied the Interaction of reactive quinone metabolites of various estrogens and of benzene with the major microtubular protein, tubulin, in a cell-free system. Covalent binding of the radioactively labeled metabolites to the a- and 13-subunit of tubulin was found to depend on the structure of the metabolite. When the adducted tubulins were tested in vitro for their ability to polymerize to microtubules, Inhibition of microtubule assembly was obsened in every case, although to varying extents. It is proposed that the fonnation of covalent tubulin adducts may impair the formation of mitotic spindies and thus contribute to chromosomal nondisjunction and aneuploidy induction.},
  subject      = {Toxikologie},
  language  = {en}
}
@article{StopperMetzler1991,
  author    = {Stopper, Helga and Metzler, M.},
  title     = {Carcinogenic oestrogens induce respiration deficiency mutation in yeast},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63466},
  year      = {1991},
  abstract  = {In addition to hormonal activity, genetic darnage has been proposed as an important factor in oestrogen-mediated carcinogenesis. However, as short-term tests for oestrogens usually fail to show DNA mutations, lesions other than dassie nuclear DNA mutation have to be considered. Oestrogeninduced mitochondrial darnage was studied in the yeast Saccharomyces cerevisiae. Stilbene-type, but not steroidal, oestrogens were found to induce respiration-dcficient petite mutation. The effect was inversely correlated with cytotoxicity and required aromatic hydroxyl groups at the stilbene molecule. It only occurred under growth conditions and apparently was not due to the A TPase inhibitory qualities of stilbene oestrogens. Other studies have shown that petite mutation clones, which can be induced by a variety of substances, contain altered mitochondrial DNA. The mechanism of petite mutation induction might be important in tumorigenesis by also acting on nuclear DNA or facilitating carcinogenesis by disturbance of mitochondrial function.},
  subject      = {Toxikologie},
  language  = {en}
}