17 ?ethynylestradiol and norgestrel in combination induce micronucleus increases and aneuploidy in human lymphocyte and fibroblast cultures

Bukvić, Nenad; Susca, Francesco; Bukvic, Dragoslav; Fanelli, Margherita; Guanti, Ginevra

doi:10.1002/(sici)1520-6866(2000)20:3<147::aid-tcm6>3.0.co;2-t

Cited by 10 publications

(4 citation statements)

References 45 publications

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“…Our results showed that when the concentration of COCPs which was given to the pregnant mice increased the chromosomal aberration percentage in the bone marrow cells or spleen cells, that because the low concentration of chemical substance didn't have the ability to reach and effects in the incur molecules which is DNA and protein, although the low concentration have the ability to repair and repeat DNA structure very fast in low concentration but high concentration work on cripple this process [6,7]. The results showed that COCPs have the ability to induce chromosomal aberration in the bone marrow cells and spleen cells in the new generation belonged to mothers treated with this drug but little much from the results of the positive control, some researchers noted that norethisterone, which it is some kind of progesterone that used in COCPs can induce chromosomal aberration in the bone marrow cells [8].…”

Section: Discussionmentioning

confidence: 74%

Cytogenetic effects of oral Contraceptive pills during pregnancy on some aspects of fetus and newborn in mice

Saeed¹,

Al-Juboori²,

Al-Nida³

2013

JoBRC

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The cytogenetic effects of taking oral contraceptive pills OCPs that contain steroid hormones (estrogen and progesterone) during pregnancy on some aspects of fetus and newborn have been previously reviewed. The objectives of this study are to detect the effect of using different doses of progestin and estrogen by pregnant female mice on the chromosomal aberration CAs and mitotic index MI in their male fetuses. Thirty female mice were divided equally into three major groups: two experimental G1 and G2 and control group according to the level of the dose. Administration of COCPs (either 0.034 or 0.068 mg/kg b. wt. /d dissolved with 0.1ml distilled water) orally once a day, were started at the first day of gestation and continued till day 14 for the experimental groups G1and G2 respectively. When the new pups in each experimental and control group reach two weeks of age, those male offspring 10animals/ group were used for chromosome preparation, while the control group divided into two groups: ten animals represented a negative control given distilled water only, while the other ten animals injected intra peritoneal with mitomycin–C 2mg/Kg represented positive control (once dose). The statistical analysis of mice bone marrow cells have no significant decrease in the mitotic index of the pups belongs to G1 mothers in comparison with negative control group, but it shows a highly significant differences P<0.01 as compared with that of positive control group . Although the pups belong to G2 mothers showed a slight decrease in the mitotic index in comparison with negative control group. Differences were non- significant with negative control and highly significant P<0.01 with positive control group. In addition, the mitotic index of spleen cells of the pups belongs to G1 mothers noticed no significant decrease in comparison with negative control group, however, it shows a significant differences P< 0.05 as compared with positive control group. In the pups belongs to G2 mothers there were significant decrease P< 0.05 in mitotic index in comparison with negative and positive control groups. The results showed that the COCPs caused an increase in chromosomal aberrations CAs with increasing of steroid hormones concentration. In G1 group the CA equal to 19.91%. This reducing in CA was not significant in comparison with those of the negative control which gave 14.33%; this percentage was increased in the result of CAs of the mice treated with mitomycin –C (MMC) which was 48.58%. Treatment with 0.068 mg/kg B wt. of COCPs gave CA equal to 17.18%. This value was not significant in comparison with those of the negative control which was 19.91%. Higher doses of OCPs may cause cytogenetic effects in chromosomal aberrations CAs and decrease the mitotic index (MI) in the bone marrow cells and spleen cells of offspring belonged to mothers treated with oral contraceptive during their pregnancy for 14 days.

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Section: Discussionmentioning

confidence: 74%

Cytogenetic effects of oral Contraceptive pills during pregnancy on some aspects of fetus and newborn in mice

Saeed¹,

Al-Juboori²,

Al-Nida³

2013

JoBRC

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“…Estradiol and ethinyl estradiol (synthetic derivative of estradiol) are associated in CTD with increased expression of BAX, CDKN1A, GADD45A , and MDM2 , among numerous other p53 downstream genes. Results of traditional genotoxicity studies with 17α‐ethinylestradiol using the micronucleus endpoint in vivo have yielded contradictory results (e.g., Shelby et al, ; Dhillon and Dhillon, ), while one study showed weak evidence of aneuploidy induction (centromere positive micronuclei) in human lymphocytes treated in vitro (Bukvic et al, ). Thus, the activity of these hormonal compounds in the p53RE assay may reflect a potential for multiple biological effects including genotoxicity which are dependent on the context in which the exposures occur.…”

Section: Discussionmentioning

confidence: 99%

Assessment of the DNA damaging potential of environmental chemicals using a quantitative high‐throughput screening approach to measure p53 activation

Witt

Hsieh

Smith‐Roe

et al. 2017

Environ and Mol Mutagen

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Genotoxicity potential is a critical component of any comprehensive toxicological profile. Compounds that induce DNA or chromosomal damage often activate p53, a transcription factor essential to cell cycle regulation. Thus, within the U.S. Tox21 Program, we screened a library of ~10,000 (~8,300 unique) environmental compounds and drugs for activation of the p53-signaling pathway using a quantitative high-throughput screening assay employing HCT-116 cells (p53+/+) containing a stably integrated β-lactamase reporter gene under control of the p53 response element (p53RE). Cells were exposed (-S9) for 16 h at 15 concentrations (generally 1.2 nM to 92 μM) three times, independently. Excluding compounds that failed analytical chemistry analysis or were suspected of inducing assay interference, 365 (4.7%) of 7,849 unique compounds were concluded to activate p53. As part of an in-depth characterization of our results, we first compared them with results from traditional in vitro genotoxicity assays (bacterial mutation, chromosomal aberration); ~15% of known, direct-acting genotoxicants in our library activated the p53RE. Mining the Comparative Toxicogenomics Database revealed that these p53 actives were significantly associated with increased expression of p53 downstream genes involved in DNA damage responses. Furthermore, 53 chemical substructures associated with genotoxicity were enriched in certain classes of p53 actives, e.g., anthracyclines (antineoplastics) and vinca alkaloids (tubulin disruptors). Interestingly, the tubulin disruptors manifested unusual non-monotonic concentration response curves suggesting activity through a unique p53 regulatory mechanism. Through analysis of our results, we aim to define a role for this assay as one component of a comprehensive toxicological characterization of large compound libraries.

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“…Fifty metaphases were scored for SCE analysis, and at least 200 mitoses were calculated for the proliferative rate index (PRI). A modified technique Micronucleus Test (MN; Bukvic et al, 2000) described by Fenech (1993) was used. When 80% of confluence was reached, Cytochalasin-B was added at a final concentration of 6 µg/ml.…”

Section: Methodsmentioning

confidence: 99%

“…Fetal cells were used to evaluate the influence of PCS on the SCE and MN frequency. For the SCE analysis, 5-Deoxybromouridine (BrdU) 10 µg/ml (Bukvic et al, 2000;Gebhart, 1981;Lukusa et al, 1988;) was added for the culture period (48 hours and 72 hours). For the final 2 hours, the cells were exposed to Colcemid, at a final concentration of 0.2 µg/ml.…”

Section: Methodsmentioning

confidence: 99%

SCE Frequency Measurement Could Be Useful in the Prenatal Diagnosis of Roberts Syndrome

et al. 2007

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In a previously published article (Resta et al., 2006) on Robert's syndrome in prenatal diagnosis, a case of a 36-year-old woman and her 36-year-old, nonconsanguineous husband were presented. Our findings suggest the existence of nonsense mediated decay (NMD) variability which could account for the varying severity reported in carriers of identical mutations. Furthermore, fetal cells were used to evaluate the influence of premature centromere separation (PCS) on the sister chromatid exchange (SCE) and micronucleus (MN) frequency. Given the similar variation observed in the SCE frequencies, dependent on tissue/cell type (amniotic fluid sample, chorionic villus sampling) and duration of in vitro cultures (48 hours or 72 hours), the idea was that this new piece of information could be interesting. It seems that the SCE frequency increased proportionally to the cell cycle increasing (1° < 2° < 3° … n). Obviously, our observations are too scarce to draw conclusions, but further investigation could be useful to corroborate or dispute these results, considering that the two techniques, (MN and SCE), are simple to perform and do not require expensive laboratory equipment.

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17 ?ethynylestradiol and norgestrel in combination induce micronucleus increases and aneuploidy in human lymphocyte and fibroblast cultures

Cited by 10 publications

References 45 publications

Cytogenetic effects of oral Contraceptive pills during pregnancy on some aspects of fetus and newborn in mice

Cytogenetic effects of oral Contraceptive pills during pregnancy on some aspects of fetus and newborn in mice

Assessment of the DNA damaging potential of environmental chemicals using a quantitative high‐throughput screening approach to measure p53 activation

SCE Frequency Measurement Could Be Useful in the Prenatal Diagnosis of Roberts Syndrome

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