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Genotoxic potential of estrogens
B S Hundal1, V S Dhillon, I S Sidhu
1Department of Public Health, National Institutes of Health, Bethesda, MD, USA.
Abstract:
A genotoxicity evaluation of three commonly used estrogens-ethinyl estradiol, cyclotriol and cyclodiol was undertaken using short-term in vitro and in vivo assays. None of the drugs caused significantly increased or decreased number of His+ mutants to appear in the Ames Salmonella assay, either with or without S9 mix or in a modified host-mediated version of this assay. However, the clastogenic potential of these drugs became evident from the increased number or chromosome aberrations and sister chromatid exchanges (SCEs) induced by these drugs in human lymphocyte cultures both in the presence and absence of S9 mix. Increased frequencies of micronuclei and of sister chromatid exchanges in mice confirmed their clastogenic potential.
Insights
Three common estrogens showed no mutagenic effects in the Ames test. However, ethinyl estradiol, cyclotriol, and cyclodiol demonstrated clastogenic potential, causing chromosome damage in human cells and mice.
Area of Science:
- Toxicology
- Genetics
- Endocrinology
Background:
- Estrogens are widely used in medicine and hormone replacement therapy.
- Assessing the genotoxicity of commonly used pharmaceuticals is crucial for public health.
- Previous genotoxicity data for some estrogens may be limited or inconclusive.
Purpose of the Study:
- To evaluate the genotoxic potential of three common estrogens: ethinyl estradiol, cyclotriol, and cyclodiol.
- To determine if these estrogens induce mutations or chromosomal damage.
- To assess genotoxicity using both in vitro and in vivo assays.
Main Methods:
- Ames Salmonella assay (bacterial reverse mutation test) with and without metabolic activation (S9 mix).
- In vitro assays using human lymphocyte cultures to assess chromosome aberrations and sister chromatid exchanges (SCEs).
- In vivo assays in mice to evaluate micronuclei formation and SCEs.
Main Results:
- No significant mutagenic activity was observed in the Ames Salmonella assay for any of the tested estrogens.
- All three estrogens induced a significant increase in chromosome aberrations and SCEs in human lymphocytes.
- In vivo studies confirmed the clastogenic potential, with increased frequencies of micronuclei and SCEs observed in mice.
Conclusions:
- Ethinyl estradiol, cyclotriol, and cyclodiol do not exhibit mutagenic properties.
- These estrogens possess clastogenic potential, indicating they can induce chromosomal damage.
- Further investigation into the long-term implications of estrogen-induced clastogenicity is warranted.