Significance of Rat Mammary Tumors for Human Risk Assessment

Russo, José

doi:10.1177/0192623314532036

Cited by 75 publications

(99 citation statements)

References 129 publications

(224 reference statements)

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“…NMU induced palpable tumors exhibit a wide spectrum of pathology ranging from fibroadenomas, adenomas, to Type I and II papillary carcinomas, 33 often with characteristics of each in surrounding breast tissue (Supporting Information Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

Effect of a tissue selective estrogen complex on breast cancer: Role of unique properties of conjugated equine estrogen

Yue

Wang

Atkins

et al. 2018

Intl Journal of Cancer

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The Women's Health Initiative studies reported that the menopausal hormone therapy (MHT) regimen containing conjugated equine estrogen (CEE) and medroxyprogesterone acetate increased, whereas CEE alone reduced breast cancer incidence. These observations suggest the possibility that CEE might exert unique actions on breast and also suggest the need to eliminate the progestogen from MHT regimens. A MHT regimen called a tissue selective estrogen complex (TSEC), containing CEE plus bazedoxifene (BZA), to avoid the need for a progestogen, was developed and FDA approved. Our study addressed two questions regarding this TSEC: (i) whether CEE exert effects on breast cancer which differ from those of estradiol (E ) and (ii) whether BZA antagonize the effects of E and CEE on breast cancer? Two rodent models (NMU and ACI) were used to compare the effect of CEE with E on mammary tumor formation, proliferation and apoptosis. In both the NMU and ACI models, E significantly increased tumor incidence and multiplicity whereas in striking contrast CEE did not, even though the estrogenic effects of CEE and E on uterine weight were identical. Mechanistically E blocked whereas CEE stimulated apoptosis (cleaved caspase-3) in ACI animals and only E stimulated proliferation (Ki67). BZA exerted highly potent anti-estrogenic effects on tumors by completely blocking palpable tumor formation. These data suggest that the CEE/BZA TSEC may be a safer, breast-antagonistic, MHT agent for women and might have potential to prevent breast cancer while relieving menopausal symptoms.

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Section: Resultsmentioning

confidence: 99%

Effect of a tissue selective estrogen complex on breast cancer: Role of unique properties of conjugated equine estrogen

Yue

Wang

Atkins

et al. 2018

Intl Journal of Cancer

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“…In fact, TEBs continued to develop in all three strains as evidenced by the increase in TEB/mm from PND25 to PND45. This is important as tumor type and incidence are directly related to the number of TEBs present at the time of carcinogen administration in tumor inducing studies (Russo 2015). The administration of DMBA while undifferentiated TEBs are present induces excessive proliferation of TEBs into intraductal proliferations which leads to the formation of ductal carcinomas (Russo 2015).…”

Section: Discussionmentioning

confidence: 99%

Differences in the Rate of in Situ Mammary Gland Development and Other Developmental Endpoints in Three Strains of Female Rat Commonly Used in Mammary Carcinogenesis Studies

et al. 2016

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The potential of chemicals to alter susceptibility to mammary tumor formation is often assessed using a carcinogen-induced study design in various rat strains. The rate of mammary gland development must be considered so that the timing of carcinogen administration is impactful. In this study, in situ mammary gland (MG) development was assessed in females of the Harlan Sprague Dawley (Hsd:SD), Charles River Sprague Dawley (Crl:SD), and Charles River Long Evans (Crl:LE) rat strains at postnatal day (PND) 25, 33, and 45. Development was evaluated by physical assessment of growth parameters, developmental scoring, and quantitative morphometric analysis. Though body weight was consistently lower and day of vaginal opening (VO) occurred latest in female Hsd:SD rats, they exhibited accelerated pre-and peripubertal MG development compared to other strains. Glands of Crl:SD and Crl:LE rats exhibited significantly more terminal end buds (TEBs) and TEB/mm than Hsd:SD rats around the time of VO. These data suggest a considerable difference in rate of MG development across commonly used strains, which is independent of body weight and timing of VO. In mammary tumor induction studies employing these strains, administration of the carcinogen should be timed appropriately, based on strain, to specifically target the peak of TEB occurrence.

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“…This is a classical model of breast carcinogenesis and is based on the high susceptibility of Sprague‐Dawley female rats to initiation with a single dose of this chemical carcinogen. In addition, most of the neoplastic lesions found in Sprague‐Dawley rat mammary glands have their counterparts in human pathology . Animals were examined for mammary tumor development three times a week by palpation.…”

Section: Methodsmentioning

confidence: 99%

Paternal selenium deficiency but not supplementation during preconception alters mammary gland development and 7,12‐dimethylbenz[a]anthracene‐induced mammary carcinogenesis in female rat offspring

Guido

Fontelles

Rosim

et al. 2016

Intl Journal of Cancer

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Breast cancer is a global public health problem and accumulating evidence indicates early-life exposures as relevant factors in the disease risk determination. Recent studies have shown that paternal nutrition can influence offspring health including breast cancer risk. Selenium is a micronutrient with essential role in central aspects of embryogenesis, male fertility and cancer and that has been extensively studied as a chemopreventive agent in several breast cancer experimental models. Thus, we designed an animal study to evaluate whether paternal selenium deficiency or supplementation during preconception could affect the female offspring mammary gland development and breast cancer susceptibility. Male Sprague-Dawley rats were fed AIN93-G diet containing 0.15 ppm (control diet), 0.05 ppm (deficient diet) or 1 ppm (supplemented diet) of selenium for 9 weeks and mated with control female rats. Mammary carcinogenesis was induced with 7,12-dimethylbenz[a]anthracene (DMBA) in their female offspring. Paternal selenium deficiency increased the number of terminal end buds, epithelial elongation and cell proliferation in the mammary gland of the female rat offspring and these effects were associated with higher susceptibility to DMBA-induced mammary tumors (increased incidence and higher grade tumors). On the other hand, paternal selenium supplementation did not influence any of these parameters. These results highlight the importance of father's nutrition including selenium status as a relevant factor affecting daughter's breast cancer risk and paternal preconception as a potential developmental stage to start disease preventive strategies.

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Significance of Rat Mammary Tumors for Human Risk Assessment

Cited by 75 publications

References 129 publications

Effect of a tissue selective estrogen complex on breast cancer: Role of unique properties of conjugated equine estrogen

Effect of a tissue selective estrogen complex on breast cancer: Role of unique properties of conjugated equine estrogen

Differences in the Rate of in Situ Mammary Gland Development and Other Developmental Endpoints in Three Strains of Female Rat Commonly Used in Mammary Carcinogenesis Studies

Paternal selenium deficiency but not supplementation during preconception alters mammary gland development and 7,12‐dimethylbenz[a]anthracene‐induced mammary carcinogenesis in female rat offspring

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