DNA clastogenic activity of diethylstilbestrol

DES can lead to DNA damage

1985 Study Abstract

Incubation of human leukocytes with the synthetic estrogen and known human carcinogen, diethylstilbestrol (DES), for 40 min caused extensive DNA strand breakage (clastogenesis), as measured by a fluorometric assay.

The level of DNA clastogenesis was dose dependent above an apparent threshold of 10 microM. Clastogenesis was increased by addition of cysteamine, a reducing agent and hydroxyl radical scavenger, and was blocked by low concentrations of plasma. DES epoxide, a weakly estrogenic derivative, was about one-tenth as potent as a DNA clastogen.

Unexpected and paradoxical findings were observed when cells were treated with DES in the presence of a hydrogen peroxide-generating system plus a peroxidase. At the subthreshold concentration of 10 microM DES, the oxidizing system increased DNA clastogenicity, yet at 30 microM DES the oxidizing system decreased clastogenicity. The addition of superoxide dismutase to the oxidizing system increased clastogenicity at both concentrations of DES. DNA damage was largely blocked by arsenite, N-ethylmaleimide, iodoacetamide and bromophenacyl bromide.

These experiments provide further indication of the complex nature of reactions involving DES which can lead to DNA damage and which may be relevant to DES-induced carcinogenesis.

Sources and more information
  • DNA clastogenic activity of diethylstilbestrol, Biochemical pharmacology, NCBI PubMed PMID: 3876097, 1985 Sep 15.
  • DNA featured image credit Erik Schepers.

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