TY  - JOUR
A1  - Viviani, A.
A1  - Däniken, A. von
A1  - Schlatter, C.
A1  - Lutz, Werner K.
T1  - Effect of selected induction of microsomal and nuclear aryl hydrocarbon monooxygenase and epoxide hydrolase as well as cytoplasmic glutathione S-epoxide transferase on the covalent binding of the carcinogen benzo(a)pyrene to rat liver DNA in vivo
N2  - Groups of four adult male rats [ZUR:SIV -Z] were pretreated with corn oil (control; 2 ml/kg/day i. p. for 3 days), trans-stilbene-oxide (SO; 200 mg/kg/day i. p. for 2 days), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 10 \(\mu\)g/kg i. p. once, 4 days before killing), phenobarbital (PB; 1 gjliter in the drinking water for 8 days), and dieldrin (20 mg/kg/day i. p. for 3 or 9 days). They received an injection of [G-\(^3\)H]benzo(a)pyrene (BaP, 31 \(\mu\)g/kg, 7.4. 10\(^9\) dpm/kg; i. v.) 16 h before killing. In the liver of each rat, five enzymatic activities and the covalent binding of BaP to DNA have been determined. The rnicrosomal aryl hydrocarbon monooxygenase activity (AHM) ranged frorn 75% of control (SO) to 356% (TCDD), the nuclear AHM from 63% (SO) to 333% (TCDD). Microsomal epoxide hydrolase activity (EH) was induced up to 238% (PB), nuclear EH ranged from 86% (TCDD) to 218% (PB). A different extent of induction was observed in the two compartments. Highest induction of glutathione S-epoxide transferase activity (GST) was found with PB (202%). The DNA binding of BaP was modulated within 79% (dieldrin, 9 days) and 238% of control (TCDD). An enzyme digest of control DNA was analysed by Sephadex LH-20 chromatography. Multiple linear regression analysis with all data expressedas o/o of control yielded the following equation: DNA Binding = 1.49 · Microsomal AHM- 1.07 · Nuclear AHM+ 0.33 · Microsomal EH- 0.52 · N uclear EH+ 0.11 · Cytoplasmic GST + 58.2. From this analysis it is concluded that (1) AHM located in the endoplasmic reticulum is most important in the formation of DNA-binding metabolites, (2) EH in the same compar.tment is not determinative in thls respect nor has it a protective effect, (3) both membrane-bound enzyme activities located in the nucleus may inactivate potential ultimate carcinogens, and ( 4) cytoplasmic GST probably cannot reduce DNA binding due to its subcellular localization.
KW  - Toxikologie
KW  - Carcinogen
KW  - Benzo(a)pyrene-DNA binding
KW  - Enzyme induction
KW  - Aryl hydrocarbon rnonooxygenase
KW  - Epoxide hydrolase
KW  - Glutathione Stransferase
Y1  - 1980
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61114
ER  - 
TY  - JOUR
A1  - Lutz, Werner K.
A1  - Schlatter, C.
T1  - In vivo covalent binding of chemicals to DNA as a short-term test for carcinogenicity
N2  - 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.
KW  - DNA
KW  - DNA-Binding
KW  - Carcinogen
KW  - Short-term Carcinogenicity Test
KW  - Aflatoxin
KW  - Toluene
KW  - Tritiated Water
Y1  - 1979
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-80127
ER  - 
TY  - JOUR
A1  - Caviezel, M.
A1  - Aeschbach, A. P.
A1  - Lutz, Werner K.
A1  - Schlatter, C.
T1  - Reduction of covalent binding of aflatoxin B1 to rabbit liver DNA after immunization against this carcinogen
N2  - 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.
KW  - Krebs
KW  - DNA
KW  - Aflatoxin
KW  - Cancer prevention
KW  - Carcinogen
KW  - Covalent binding
KW  - DNA
KW  - Immunization
Y1  - 1984
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-80116
ER  -