@article{BaertschLutzSchlatter1991,
  author    = {Baertsch, A. and Lutz, Werner K. and Schlatter, C.},
  title     = {Effect of inhalation exposure regimen on DNA binding potency of 1,2-dichloroethane in the rat},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-60743},
  year      = {1991},
  abstract  = {1 ,2-Dichloroethane (DCE) was reported to be carcinogenic in rats in a long-tenn bioassay using gavage in com oil (24 and 48 mg/kg/day), but not by inhalation (up to 150-250 ppm, 7 h/day, 5 days/week). The daily dose metabolized was similar in the two experiments. In order to address this discrepancy, the genotoxicity of DCE was investigated in vivo under different exposure conditions. Fernale F-344 rats (183-188 g) were exposed to [1,2-14C]DCE in a closed inhalation chamber to either a low, constant concentration (0.3 mg/l = 80 ppm for 4 h) or to a peak concentration (up to 18 mg/1 = 4400 ppm) for a few minutes. After 12 h in the chamber, the dose metabolized under the two conditions was 34 mg/kg and 140 mg/k:g. DNA was isolated from liver and lung and was purified to constant specific radioactivity. DNA was enzymaticaBy hydrolyzed to the 3' -nucleotides which were separated by reverse phase HPLC. Most radioactivity eluted without detectable or with little optical density' indicating that the major part of the DNA radioactivity was due to covalent binding of the test compound. The Ievel of DNA adducts was expressed in the dose-nonnalized units ofthe Covalent Binding Index, CBI = f.Lmol adduct per mol DNA nucleotide/ mmol DCE per kg body wt. In liver DNA, the different exposure regimens resulted in markedly different CBI values of 1.8 and 69, for "constant-low" and ''peak" DCE exposure Ievels. In the Jung, the respective values were 0.9 and 31. It is concluded that the DNA darnage by DCE depends upon the concentration-time profile and that the carcinogenic potency determined in the gavage study should not be used for low-Ievel inhalation exposure.},
  subject      = {Toxikologie},
  language  = {en}
}
@article{CaviezelAeschbachLutzetal.1984,
  author    = {Caviezel, M. and Aeschbach, A. P. and Lutz, Werner K. and Schlatter, C.},
  title     = {Reduction of covalent binding of aflatoxin B1 to rabbit liver DNA after immunization against this carcinogen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-80116},
  year      = {1984},
  abstract  = {The covalent binding of [3H]aflatoxin B1 (AF) to liver DNA was determined, 6 h after oral administration to male rabbits. A Covalent Binding Index, CBI (flmol AF/mol DNA-P)/(mmol AF/kg b. w.) = 8,500 was found. Pretreatment of rabbits with AF coupled to bovine serum albumin in Freund's adjuvant led to the production of AF-directed antibodies. Administration of [3H]AF to such immunized rabbits resulted in a CJH of only 2,500, i.e., the iiDJ{.lUnization provided a protection by a factor of more than 3. Although this is encouraging evidence for the potential of active immunization against genotoxic carcinogens, a nurober of pointswill have to be clarified, such as the time course for the DNA binding and the question of a possible shift to other target cells.},
  subject      = {Krebs},
  language  = {en}
}
@article{LutzSchlatter1979,
  author    = {Lutz, Werner K. and Schlatter, C.},
  title     = {In vivo covalent binding of chemicals to DNA as a short-term test for carcinogenicity},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-80127},
  year      = {1979},
  abstract  = {The determination of a covalent binding of radioactive chemieals to DNA in intact mammalian organisms is proposedas a short-term test for carcinogenicity. The effectiveness of covalent binding to rat liver DNA correlates well with the hepatocarcinogenicity known from long-term bioassays. The binding indices range over more than five orders of rriagnitude between the strongest hepatocarcinogen aflatoxin B 1 and the limit of detection of a binding with 100 f-LCi 14C-labelled chemical. The order of magnitude of binding is therefore a surprisingly good quantitative measure for carcinogenicity. The pattern of DNA binding sites is important especially for small alkylating agents where the determination of total binding might indicate a higher carcinogenic potency than is actually observed.},
  subject      = {DNA},
  language  = {de}
}