TY  - JOUR
A1  - Lutz, Werner K.
A1  - Jaggi, W.
A1  - Schlatter, C.
T1  - Covalent binding of diethylstilbestrol to DNA in rat and hamster liver and kidney [Short Communication]
N2  - No abstract available
KW  - Toxikologie
KW  - Carcinogenesis
KW  - Covalent binding index - Diethylstilbestrol
KW  - DNA binching
KW  - Estrogen
KW  - Hormone
Y1  - 1982
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61066
ER  - 
TY  - JOUR
A1  - Caviezel, M.
A1  - Lutz, Werner K.
A1  - Minini, U.
A1  - Schlatter, C.
T1  - Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro
N2  - (6,7-\(^3\)H] Estrone (E) and [6,7-\(^3\)H]estradiol-17ß (E\(_2\)) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E\(_2\) were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 \(\mu\)g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (\(\mu\)mol chemical bound per mol Similar considerations can be made for the liver where any true covalent DNA binding must be below a Ievel of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding. DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E\(_2\) respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E\(_2\) respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by' two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3 ,000 tim es high er than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate. Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10\(^3\)-10\(^4\) have been found for potent, 10\(^2\) for moderate, and 1-10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured Iimit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action.
KW  - Toxikologie
KW  - Estrogen
KW  - Hormone
KW  - Carcinogenesis
KW  - DNA binding
KW  - Protein binding
KW  - Estrone
Y1  - 1984
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60995
ER  -