MUTAGENIC AND RECOMBINAGENIC EFFECTS OF DIETHYLSTILBESTROL QUINONE

Estrogens are believed to be major contributors to many cancers of the human female genital tract, but the mechanism of their carcinogenic a ction is not well-understood. While a tumor-promoting role for estroge ns is well-supported, whether they also act as tumor initiators has re mained controversial. Here, we have sought to examine the mutagenic po tential of diethylstilbestrol, a synthetic estrogen that is a powerful carcinogen in hamsters, and is suspected to be a human carcinogen. Ph age M13 single-stranded DNA was treated in vitro with diethylstilbestr ol quinone (DES Q; 1.25 mM) and transfected into Escherichia coli cell s. DES Q treatment resulted in an apparent enhancement of mutagenesis in the LacZ(alpha) gene segment. DNA sequence analysis of LacZ(alpha) mutants obtained by transfection of DES Q-treated DNA revealed that th e major effect of DES Q treatment has been a 6-fold elevation of recom bination between the phage-borne LacZ(alpha) sequence and the LacZDELT AM15 sequence on the E. coli fertility plasmid F. To confirm whether D ES Q treatment is recombinagenic, we used an experimental system that allows the detection of recombination between a defective E. coli chro mosomal LacY gene and a normal counterpart borne on a plasmid. Transfe ction of DES Q (0.06-12 mM) treated plasmid DNA showed significant enh ancement (2-100-fold) in recombination, but not in mutagenesis. These results raise the possibility that estrogen quinones may induce recomb inagenic DNA damage.