title: Mutagenic and recombinagenic effects of diethylstilbestrol quinone.
abstract: Estrogens are believed to be major contributors to many cancers of the human female genital tract, but the mechanism of their carcinogenic action is not well-understood. While a tumor-promoting role for estrogens is well-supported, whether they also act as tumor initiators has remained controversial. Here, we have sought to examine the mutagenic potential of diethylstilbestrol, a synthetic estrogen that is a powerful carcinogen in hamsters, and is suspected to be a human carcinogen. Phage M13 single-stranded DNA was treated in vitro with diethylstilbestrol quinone (DES Q: 1.25 mM) and transfected into Escherichia coli cells. 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 the major effect of DES Q treatment has been a 6-fold elevation of recombination between the phage-borne LacZ(alpha) sequence and the LacZ delta M15 sequence on the E. coli fertility plasmid F. To confirm whether DES Q treatment is recombinagenic, we used an experimental system that allows the detection of recombination between a defective E. coli chromosomal LacY gene and a normal counterpart borne on a plasmid. Transfection of DES Q (0.06-12 mM) treated plasmid DNA showed significant enhancement (2-100-fold) in recombination, but not in mutagenesis. These results raise the possibility that estrogen quinones may induce recombinagenic DNA damage.
authors.affiliation: Department of Microbiology and Molecular Genetics, UMD-New Jersey Medical School, Newark 07103.
authors.forename: R M
authors.initials: RM
authors.lastname: Korah
authors.forename: M Z
authors.initials: MZ
authors.lastname: Humayun
mesh_terms: D017104:Bacteriophage M13 / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D004249:DNA Damage; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000187:drug effects; D004277:DNA, Single-Stranded / Q000187:drug effects; D004279:DNA, Viral / Q000187:drug effects; D004054:Diethylstilbestrol / Q000031:analogs & derivatives* / Q000633:toxicity; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D005144:F Factor / Q000187:drug effects; D007763:Lac Operon / Q000187:drug effects; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity*; D010957:Plasmids; D017354:Point Mutation; D011995:Recombination, Genetic / Q000187:drug effects*; D017384:Sequence Deletion; D014162:Transfection
chemical_list: D004269:DNA, Bacterial; D004277:DNA, Single-Stranded; D004279:DNA, Viral; D009153:Mutagens; C039998:diethylstilbestrol quinone; D004054:Diethylstilbestrol