Mutagenic and recombinagenic effects of diethylstilbestrol quinone

Reju M. Korah, M. Zafri Humayun

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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(α) gene segment. DNA sequence analysis of LacZ(α) 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(α) sequence and the LacZΔM15 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.

Original languageEnglish (US)
Pages (from-to)205-214
Number of pages10
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume289
Issue number2
DOIs
StatePublished - Oct 1993

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

Keywords

  • Diethylstilboestrol quinone
  • Escherichia coli
  • Hormonal carginogenesis
  • Oestrogens
  • genetic effects

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