Does DES exposure induce recombinagenic DNA damage ?
1993 Study 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.
- Mutagenic and recombinagenic effects of diethylstilbestrol quinone, European journal of cancer, Mutation research, NCBI PubMed PMID : 7690889, Oct 1993.
- Isolated LacZ featured image credit igem Team Michigan Results.