Abstract
Past research has demonstrated that oestrogenic compounds produce strand breaks in the DNA of sperm and lymphocytes via reactive oxygen species (ROS). In the current investigation, sperm and lymphocytes were treated in vitro with oestrogenic compounds (diethylstilboestrol, progesterone, 17β-oestradiol, noradrenaline and triiodotyronine) and several aspects of DNA damage were investigated. Firstly, mediation of DNA damage by lipid peroxidation was investigated in the presence of BHA (a lipid peroxidation blocker). BHA reduced the DNA damage generated by 17β-oestradiol and diethylstilboestrol in a statistically significant manner. No effects were observed for sperm. Secondly, the presence of oxidized bases employing FPG and EndoIII were detected for lymphocytes and sperm in the negative control and after 24 h recovery in lymphocytes but not immediately after treatment for both cell types. The successful detection of oxidized bases in the negative control (untreated) of sperm provides an opportunity for its application in biomonitoring studies. DNA repair at 24 h after exposure was also studied. A nearly complete recovery to negative control levels was shown in lymphocytes 24 h recovery after oestrogenic exposure and this was statistically significant in all cases. Rapid rejoining of DNA, in a matter of hours, is a characteristic of DNA damaged by ROS.
Highlights
Oestrogens play a key role in the development of feminine characteristics, control of reproductive cycles and pregnancy, and have an influence on the skin, bone, the cardiovascular system and immunity [1]
Lipid peroxidation appears to be a major source of endogenous DNA damage in humans that may contribute significantly to cancer and other genetic diseases linked to lifestyle and dietary factors [32]
The present study reveals some possible mechanisms involved in the genotoxicity of oestrogenic compounds
Summary
Oestrogens play a key role in the development of feminine characteristics, control of reproductive cycles and pregnancy, and have an influence on the skin, bone, the cardiovascular system and immunity [1]. Exposure to oestrogens and oestrogen-like compounds has been associated with the development of cancer and other effects [2]. A strong positive association between breast cancer risk and circulating levels of both oestrogens and androgens has been confirmed [3,4]. Epidemiological data implicate an imbalance of oestrogens and progestogens in the etiology of endometrial cancer [5]. The Women’s Health Initiative Study demonstrated that women receiving hormone replacement therapy (HRT), consisting of oestrogen plus progestin, have an increased risk of endometrial and invasive breast carcinoma [6]. Oestrogens have been implicated in the development of prostate cancer [10,11]
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