Cyproterone acetate is an integral part of hepatic DNA adducts induced by this steroidal drug.
We have recently shown that cyproterone acetate (CPA), an active component of some antiandrogenic drugs, induces the formation of DNA adducts detectable by the 32P-DNA postlabelling technique in rat liver. The postlabelling technique, however, does not provide evidence for the chemical nature of the adducts observed. To ascertain whether the CPA-induced adducts do contain CPA, we have incubated tritiated CPA with cultured hepatocytes from female rats, digested the DNA to 3'-monophosphonucleosides, extracted the DNA adducts formed into butanol and phosphorylated the adducts in the extract with unlabelled ATP. One major and one minor 3H-labelled adduct spot were detectable on the TLC chromatograms. The spots appeared at positions identical to those observed in the 32P-postlabelling experiments with unlabelled CPA. Furthermore, the ratio of 3H activity for the major versus the minor adduct spot was 11.9 +/- 1.8, which agreed with the corresponding ratio for the 32P activities, which was 13.2 +/- 3.5. These findings indicate that the CPA-induced DNA adducts, which we have previously detected by 32P-postlabelling do contain CPA or CPA metabolites.
Topinka
J
J
Regional Hygiene Institute of Central Bohemia, Praha, Czech Republic.
Binkova
B
B
Schwarz
L R
LR
Wolff
T
T
D000726:Androgen Antagonists / Q000378:metabolism*; D000818:Animals; D017373:Cyproterone Acetate / Q000378:metabolism*; D018736:DNA Adducts / Q000032:analysis*; D005260:Female; D008099:Liver / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000726:Androgen Antagonists; D018736:DNA Adducts; D017373:Cyproterone Acetate