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Charles River Sprague Dawley rats lack early age-dependent susceptibility to DMBA-induced mammary carcinogenesis.

Gear RB, Yan M, Schneider J, Succop P, Heffelfinger SC, Clegg DJ - Int. J. Biol. Sci. (2007)

Bottom Line: Here we demonstrate, rather than the classical U-shaped dose curve in which there is maximum sensitivity for DMBA at 50 days, there is an increasing degree of sensitivity with age in the CD(R) IGS rat.Additionally, we report that vehicle-treated animals developed mammary CIS without any known initiator, and 100 day virgin animals demonstrated lactational changes, independent of DMBA exposure or dose.We conclude this strain of Charles River Sprague Dawley rats has prolactin-induced pituitary stimulation, and therefore, the window of susceptibility for mammary tumorigenesis is absent.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, University of Cincinnati, PO Box 670559, Cincinnati, OH 45267-0559, USA.

ABSTRACT
Developmental stages of mammary glands influence their susceptibility to initiating events related to carcinogenesis. The "window of susceptibility" to mammary carcinogenesis is classically defined as the time in early puberty when the mammary gland morphology is most sensitive to initiation events. Administration of the polyaromatic hydrocarbon, 7,12-dimethylbenz(a)anthracene (DMBA), in a single oral dose yields maximal mammary tumor formation when administered in this "window". We examined the DMBA treated mammary glands, precursor lesions, and morphology of the uninvolved mammary epithelium for the first 100 days of life for Charles River Sprague Dawley CD(R) IGS. Our goal was to determine the DMBA dose at which 50% of the rats (IC50) developed carcinoma in situ (CIS) within three months of dosing. Here we demonstrate, rather than the classical U-shaped dose curve in which there is maximum sensitivity for DMBA at 50 days, there is an increasing degree of sensitivity with age in the CD(R) IGS rat. Additionally, we report that vehicle-treated animals developed mammary CIS without any known initiator, and 100 day virgin animals demonstrated lactational changes, independent of DMBA exposure or dose. Lastly, we demonstrate this strain of virgin female rats has elevated pituitary prolactin immunoreactivity independent of the level of mammary differentiation. We conclude this strain of Charles River Sprague Dawley rats has prolactin-induced pituitary stimulation, and therefore, the window of susceptibility for mammary tumorigenesis is absent.

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Related in: MedlinePlus

Panels (a), (b), and (c) show mammary morphology from animals at (a) 21 days, (b) 50 days, and (c) 100 days.
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Figure 5: Panels (a), (b), and (c) show mammary morphology from animals at (a) 21 days, (b) 50 days, and (c) 100 days.

Mentions: Given the morphological correlates related to the early mammary gland susceptibility, we examined rat mammary gland 4 whole mounts for developmental characteristics at the ages in which we had given DMBA (21, 50 and 100 days). These data are summarized in Figure 5. As predicted by the lactational phenotype, at 100 days of age there is significantly advanced lobular maturation in the mammary gland with numerous type 2 lobules and even a few type 3 lobules, reminiscent of a pseudopregnant state. All of the animals at 100 days of age had fluid filled lobules and fat globules within the epithelium, but none had undergone the proliferation necessary to form fully lactational type 4 lobules.


Charles River Sprague Dawley rats lack early age-dependent susceptibility to DMBA-induced mammary carcinogenesis.

Gear RB, Yan M, Schneider J, Succop P, Heffelfinger SC, Clegg DJ - Int. J. Biol. Sci. (2007)

Panels (a), (b), and (c) show mammary morphology from animals at (a) 21 days, (b) 50 days, and (c) 100 days.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2017109&req=5

Figure 5: Panels (a), (b), and (c) show mammary morphology from animals at (a) 21 days, (b) 50 days, and (c) 100 days.
Mentions: Given the morphological correlates related to the early mammary gland susceptibility, we examined rat mammary gland 4 whole mounts for developmental characteristics at the ages in which we had given DMBA (21, 50 and 100 days). These data are summarized in Figure 5. As predicted by the lactational phenotype, at 100 days of age there is significantly advanced lobular maturation in the mammary gland with numerous type 2 lobules and even a few type 3 lobules, reminiscent of a pseudopregnant state. All of the animals at 100 days of age had fluid filled lobules and fat globules within the epithelium, but none had undergone the proliferation necessary to form fully lactational type 4 lobules.

Bottom Line: Here we demonstrate, rather than the classical U-shaped dose curve in which there is maximum sensitivity for DMBA at 50 days, there is an increasing degree of sensitivity with age in the CD(R) IGS rat.Additionally, we report that vehicle-treated animals developed mammary CIS without any known initiator, and 100 day virgin animals demonstrated lactational changes, independent of DMBA exposure or dose.We conclude this strain of Charles River Sprague Dawley rats has prolactin-induced pituitary stimulation, and therefore, the window of susceptibility for mammary tumorigenesis is absent.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, University of Cincinnati, PO Box 670559, Cincinnati, OH 45267-0559, USA.

ABSTRACT
Developmental stages of mammary glands influence their susceptibility to initiating events related to carcinogenesis. The "window of susceptibility" to mammary carcinogenesis is classically defined as the time in early puberty when the mammary gland morphology is most sensitive to initiation events. Administration of the polyaromatic hydrocarbon, 7,12-dimethylbenz(a)anthracene (DMBA), in a single oral dose yields maximal mammary tumor formation when administered in this "window". We examined the DMBA treated mammary glands, precursor lesions, and morphology of the uninvolved mammary epithelium for the first 100 days of life for Charles River Sprague Dawley CD(R) IGS. Our goal was to determine the DMBA dose at which 50% of the rats (IC50) developed carcinoma in situ (CIS) within three months of dosing. Here we demonstrate, rather than the classical U-shaped dose curve in which there is maximum sensitivity for DMBA at 50 days, there is an increasing degree of sensitivity with age in the CD(R) IGS rat. Additionally, we report that vehicle-treated animals developed mammary CIS without any known initiator, and 100 day virgin animals demonstrated lactational changes, independent of DMBA exposure or dose. Lastly, we demonstrate this strain of virgin female rats has elevated pituitary prolactin immunoreactivity independent of the level of mammary differentiation. We conclude this strain of Charles River Sprague Dawley rats has prolactin-induced pituitary stimulation, and therefore, the window of susceptibility for mammary tumorigenesis is absent.

Show MeSH
Related in: MedlinePlus