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 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.
Korah
R M
RM
Department of Microbiology and Molecular Genetics, UMD-New Jersey Medical School, Newark 07103.
Humayun
M Z
MZ
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
D004269:DNA, Bacterial; D004277:DNA, Single-Stranded; D004279:DNA, Viral; D009153:Mutagens; C039998:diethylstilbestrol quinone; D004054:Diethylstilbestrol