Lack of genotoxicity induced by endogenous and synthetic female sex hormones in peripheral blood cells detected by alkaline comet assay

Abstract

The etiology of hormone-induced cancers has been considered to be a combination of genotoxic and epigenetic events. Currently, the Comet assay is widely used for detecting genotoxicity because it is relatively simple, sensitive, and capable of detecting various kinds of DNA damage. The present study evaluates the genotoxic potential of endogenous and synthetic sex hormones, as detected by the Comet assay. Blood cells were obtained from 12 nonsmoking and 12 smoking women with regular menstrual cycles and from 12 nonsmoking women taking low-dose oral contraceptives (OC). Peripheral blood samples were collected at three phases of the menstrual cycle (early follicular, mean follicular, and luteal phases), or at three different moments of oral contraceptive intake. Three blood samples were also collected from 12 healthy nonsmoking men, at the same time as oral contraceptive users. Results showed no significant difference in the level of DNA damage among the three moments of the menstrual cycle either in nonsmoking and smoking women, or between them. No significant difference in DNA damage was also observed among oral contraceptive users, nonusers, and men. Together, these data indicate lack of genotoxicity induced by the physiological level of the female sex hormones and OC as assessed by the alkaline Comet assay. In conclusion, normal fluctuation in endogenous sex hormones and use of low-doses of oral contraceptive should not interfere with Comet assay data when this technique is used for human biomonitoring.

Lipid damage is the best marker of oxidative injury during the cardiac remodeling process induced by tobacco smoke

“…Regarding DNA damage, several studies reported increased levels of 8-hydroxyguanine in smokers compared to nonsmokers [ 17 – 19 ]. However, conflicting results have been reported with comet assays to measure DNA damage related to ETS [ 20 – 22 ]. Hoffmann and Speit showed no significant difference in genotoxic effects in peripheral bloods cells between heavy smokers and nonsmokers [ 21 ].…”

“…8-hydroxyguanine, a biomarker of oxidative DNA damage was increased in human leukocytes, urine and lung tissue of smokers compared to nonsmokers [ 17 – 19 ]. However, other clinical and experimental studies showed no difference in DNA damage, assessed by the comet assay, in peripheral blood of human or rats exposed to tobacco smoke [ 20 – 22 ]. Likewise, plasma protein carbonyl concentration, a marker of protein oxidative damage, was increased in heavy smokers in some but not all studies [ 19 , 23 ].…”

Effect of Oral Contraceptive Pills on the Blood Serum Enzymes and DNA Damage in Lymphocytes Among Users

“…It has been suggested that induction of homo oxygenases leads to the conversion of procarcinogenes-carcinogens [43] or by stimulation of the genetically altered pre-neoplastic cells [44]. The relationship between the carcinogens and sex hormones is not very clear, however a series of or combination of genotoxic and epigenetic changes have been reported to be associated with OC users [45]. In our earlier in vitro studies synthetic progestins have been reported to generate reactive oxygen species (ROS) [27].…”

Genotoxicity assessment of fipronil (frontline plus®) in Canis familiaris

“…Genotoxicity assay. The comet assay was performed in duplicate to evaluate DNA damage in peripheral blood cells by following the guidelines (Singh et al 1988) with some modifications (Tice et al 1991, Braz & Salvadori 2007. Every step was carried out under indirect light.…”