Genotoxicity of hormonal steroids

Joosten, H. F. P.; Acker, F.A.A. van; Dobbelsteen, Diels J. van den; Horbach, G. Jean; Krajnc, E.I.

doi:10.1016/j.toxlet.2004.01.018

Cited by 66 publications

(35 citation statements)

References 84 publications

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“…As one example, transferring laboratory mice from group housing to social isolation accelerates growth of induced tumors and attenuates the effects of chemotherapy (6,7). Prolonged exposure to the synthetic glucocorticoid dexamethasone has both mutagenic and clastogenic effects (8,9). In the Sprague-Dawley rat model of naturally occurring breast cancer, the magnitude of the glucocorticoid stress response was associated with mammary tumor onset, whereas time to hormonal recovery from a stressor predicted growth rate of tumors (10).…”

mentioning

confidence: 99%

Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors

Hermes¹,

Delgado²,

Tretiakova³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

179

140

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In a life span study, we examined how the social environment regulates naturally occurring tumor development and malignancy in genetically prone Sprague-Dawley rats. We randomly assigned this gregarious species to live either alone or in groups of five female rats. Mammary tumor burden among social isolates increased to 84 times that of age-matched controls, as did malignancy, specifically a 3.3 relative risk for ductal carcinoma in situ and invasive ductal carcinoma, the most common early breast cancers in women. Importantly, isolation did not extend ovarian function in late middle age; in fact, isolated animals were exposed to lower levels of estrogen and progesterone in the middle-age period of mammary tumor growth, with unchanged tumor estrogen and progesterone receptor status. Isolates, however, did develop significant dysregulation of corticosterone responses to everyday stressors manifest in young adulthood, months before tumor development, and persisting into old age. Among isolates, corticosterone response to an acute stressor was enhanced and recovery was markedly delayed, each associated with increased mammary tumor progression. In addition to being stressed and tumor prone, an array of behavioral measures demonstrated that socially isolated females possessed an anxious, fearful, and vigilant phenotype. Our model provides a framework for studying the interaction of social neglect with genetic risk to identify mechanisms whereby psychosocial stressors increase growth and malignancy of breast cancer.breast cancer ͉ glucocorticoids ͉ physiological stress ͉ psychological stress ͉ social behavior

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mentioning

confidence: 99%

Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors

Hermes¹,

Delgado²,

Tretiakova³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

179

140

View full text Add to dashboard Cite

show abstract

“…21,22) Joosten et al have suggested that 17-estradiol would lack genotoxic and carcinogenic properties in experimental models. 23) It is remarkable that 17-estradiol has generally tested negative in the ICH core battery of genotoxicity evaluation, such as the Ames test, in vitro chromosome aberration test and in vivo micronucleus test. 23) We examined the clastogenic activity of nitrite-treated 17-estradiol and 2-nitro- The concentration of each sample was 10 mM in DMSO.…”

Section: Resultsmentioning

confidence: 99%

Changes in the Mutagenic and Estrogenic Activities of 17β-Estradiol after Treatment with Nitrite

Masuda

Terashima

Sano

et al. 2006

Bioscience, Biotechnology, and Biochemistry

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“…Other important antiprogestins are mifepristone, onapristone and lilopristone which exhibit a high chemical similarity with aglepristone. No clastogenicity and no genotoxic effects of these anti-progesterone compounds had been found [21,22] . There is no information on mifepristone; on the other hand lilopristone and onapristone have been shown to be inactive in gene mutation tests [26] .…”

Section: Discussionmentioning

confidence: 97%

“…On the other hand, many exogenous hormonal steroids may cause genotoxic or cytotoxic effects and chromosome breakage [21] . Some natural estrogens, estradiol and estrone and medroxyprogesterone group of synthetic progestins with cyproterone acetate are prominent examples that are gene mutation or genotoxic activity in different tests [22] .…”

Section: Introductionmentioning

confidence: 99%

Tavşanlarda Orta Dönem Gebelikleri Sonlandırılmasında Kullanılan Bir Progesteron Antagonisti Olan Aglepriston’un Genotoksik ve Sitotoksik Etkileri

Vatan¹,

Bağdaş²,

Çinkılıç³

et al. 2015

Kafkas Univ Vet Fak Derg

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Aglepristone is an antiprogestin using for pregnancy termination in veterinary medicine. The information about side effects of aglepristone is limited. The aim of the study was to investigate cytotoxicity and genotoxicity of aglepristone in mid-gestation pregnancy termination in rabbits. Fifteen New Zealand White rabbits were used and pregnant does were randomly divided into three groups. Group I (n=5) was treated with saline as the control. The does in group II (n=5) and group III (n=5) were treated with aglepristone (10 mg/kg) on 15 th day and 15 th -16 th days of pregnancy, respectively. The rabbits were sacrificed by guillotine 24 h after last treatment. Bone marrow and blood samples were immediately collected. Cytotoxic and genotoxic potential were tested by micronucleus and Comet assays. No genotoxicity and cytotoxicity were found in micronucleus test with single aglepristone administration. In contrast, two consecutive treatments of aglepristone showed high genotoxic and cytotoxic effects on bone marrow in animals. While comet assay of blood samples did not show any significant difference between groups; the results from comet assay of bone marrow cells showed the single injection of aglepristone did not induce any DNA damage but two injections group increased the DNA damage. Keywords: Aglepristone, Cytotoxic, Genotoxic, Micronucleus test, Comet assay Tavşanlarda Orta Dönem Gebelikleri Sonlandırılmasında Kullanılan Bir Progesteron Antagonisti Olan Aglepriston'un Genotoksik ve Sitotoksik Etkileri ÖzetAglepriston, veteriner hekimlikte gebeliklerin sonlandırılmasında kullanılan bir antiprogestindir. Aglepriston'un yan etkileri ile ilgili bilgiler sınırlıdır. Çalışmamızın amacı; orta gebelikte gebeliği sonlandırılan tavşanlarda aglepriston'un potansiyel sitotoksik ve genotoksik etkilerinin araştırılmasıdır. Çalışmada 15 Yeni Zelanda beyaz tavşanı kullanılmıştır ve gebe tavşanlar rastgele üç gruba ayrıldı. I. Grup (n=5) kontrol grubu olarak tuz çözeltisi ile muamele edildi. II. Grup (n=5) gebeliğin 15. gününde aglepriston (10 mg/kg) enjekte edilen III. Grup (n=5) ise gebeliğin 15. ve 16. günlerinde aglepristone enjekte edilen gruptu. Tavşanlar son enjeksiyonlardan 24 saat sonra giyotin ile sakrifiye edilerek hızlı bir şekilde kemik iliği ve kan örnekleri alındı. Sitotoksik ve genotoksik potansiyel mikroçekirdek ve komet yöntemleri ile araştırıldı. Tek aglepriston uygulaması ile gebeliği sonlandırılan tavşanlarda mikroçekirdek testi ile herhangi bir sitotoksik ve genotoksik etki belirlenemedi. Bunun tersine iki aglepriston uygulanan tavşanların kemik iliği hücrelerinde yüksek sitotoksik ve genotoksik etki belirlendi. Komet yönteminde kullanılan kan örneklerinde gruplar arasında bir fark belirlenemedi. Kemik iliği hücrelerinin kullanıldığı komet yönteminde tek enjeksiyon grubunda herhangi bir DNA hasarı belirlenmemesine rağmen çift enjeksiyon grubunda DNA hasarının arttığı belirlendi.

show abstract

Genotoxicity of hormonal steroids

Cited by 66 publications

References 84 publications

Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors

Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors

Changes in the Mutagenic and Estrogenic Activities of 17β-Estradiol after Treatment with Nitrite

Tavşanlarda Orta Dönem Gebelikleri Sonlandırılmasında Kullanılan Bir Progesteron Antagonisti Olan Aglepriston’un Genotoksik ve Sitotoksik Etkileri

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