TRANSPLACENTAL GENOTOXICITY OF DIETHYLSTILBESTROL

Diethylstilbestrol (DES) is a transplacental carcinogen in humans and in rodents. As part of an attempt to examine the mechanism of transplacental carcinogenesis, the transplacental genotoxity of this stilbene estrogen has been investigated. Pregnant hamsters received single injections of 200 mg/kg DES on the 10th day of gestation and were killed 5 or 24 h after treatment. The maternal organs were found to contain the same DES-DNA adduct patterns observed previously by P-32-postlabeling analysis in female hamsters. These adduct patterns, generated by the genotoxic metabolite diethylstilbestrol-4',4"-quinone (DES Q), were also observed in fetal heart and kidney DNA. In fetal liver DNA, this modified nucleotide, generated by the quinone, was only the minor adduct. The major DNA adduct in this organ was not observed previously and may have been generated by an unknown DES metabolite. The data demonstrate that DES is a transplacentally active genotoxic agent. They also provide evidence for fetal metabolism of DES to DES Q and to other unknown genotoxic intermediates.