Pathogenesis of Mammary Carcinomas Induced in Rats by 7, 12-Dimethylbenz[a]anthracene2

Russo, José; Saby, Joseph; Isenberg, William M.; Russo, Irma H.

doi:10.1093/jnci/59.2.435

Cited by 122 publications

(90 citation statements)

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“…To account for this phenomenon, it generally is believed that murine mammary glands contain pluripotent stem cells, dispersed throughout the entire tissue, from which the various epithelial subtypes are generated (7,8). In support of this, in a series of elegant studies, Smith and colleagues (9)(10)(11)(12) have provided evidence that, in the mammary glands of nulliparous females, there are distinct progenitor cells for ductal vs. lobular growth, speculated to arise from a single multipotent antecedent.…”

mentioning

confidence: 99%

Impact of progesterone receptor on cell-fate decisions during mammary gland development

Shyamala

Cardiff

et al. 2000

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

127

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Mammary epithelium contains lineage-limited progenitors that give rise to cells that form distinct morphological structures, ducts vs. lobules, depending on the endocrine status of the female. Progesterone signaling through progesterone receptor (PR) is essential for lobulo-alveolar development that accompanies pregnancy, but not for ductal growth accompanying puberty. PR exists in two molecular forms, A and B, and an imbalance in the native ratio of the two isoforms can lead to alterations in PR signaling. Indeed, as we reported previously, in transgenic mice carrying additional A form of PR, mammary development is abnormal, characterized by excessive lateral ductal branching. This suggests that alterations in PR signaling may have important consequences to mammary development, particularly with regard to ductal vs. alveolar growth. To test this further, we created transgenic mice carrying additional B form of PR and report that mammary development in these mice is also abnormal, characterized by inappropriate alveolar growth. More importantly, these mammary glands, on serial transplantation, undergo a premature arrest in ductal growth without any alteration in the potential for lobulo-alveolar growth. Such an arrest in ductal growth does not occur with transgenics carrying additional A form of PR. These studies, therefore, provide strong evidence to indicate that PR signaling may be of paramount importance for appropriate cell-fate decisions during normal mammary development, and also that this requires a regulated expression of the two isoforms.

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mentioning

confidence: 99%

Impact of progesterone receptor on cell-fate decisions during mammary gland development

Shyamala

Cardiff

et al. 2000

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

127

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“…In addition, there were significantly more TEB structures in glands from PhIP-treated rats. These findings indicate that, similar to DMBA [Russo et al, 1977], a carcinogenic-dose regimen of PhIP affects mammary gland development and inhibits differentiation of TEBs to ABs. The idea that the ability to inhibit differentiation is a general property of chemical mammary gland carcinogens requires further study.…”

Section: Mammary Gland Developmentmentioning

confidence: 76%

“…Previous studies with DMBA have shown that sensitivity is correlated with the presence of mammary gland terminal end buds (TEBs) [Russo et al, 1977]. During adolescent mammary gland development, roughly between 30 and 55 days of age in the rat, numerous TEBs can be observed at the growing ends of the ductal tree.…”

Section: Mammary Gland Developmentmentioning

confidence: 99%

Mammary gland carcinogenesis by food‐derived heterocyclic amines: Metabolism and additional factors influencing carcinogenesis by 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)

Snyderwine

2002

Environ and Mol Mutagen

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The heterocyclic amines (HCAs) are a family of mutagenic/carcinogenic compounds found in cooked meats. Several HCAs are mammary gland carcinogens in rats. Of these compounds, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) is the major one present in the human diet. This report reviews the studies on rat mammary gland carcinogenesis by HCAs; discusses what is currently known regarding mechanisms of mammary gland carcinogenesis of PhIP, especially the significance of metabolic processing; and further highlights the evidence for the possible role of PhIP in human breast cancer.

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“…Due to sampling and ethical limitations intrinsic to human experimentation, what is needed is an experimental model for breast tumors which mimics the most significant aspects of the human disease. Recent studies (62,(83)(84)(85)(86) suggest that mammary carcinomas induced in Sprague-Dawley rats by 7,12-dimethylbenz(a)anthracene (DMBA) constitutes such a model. DMBA-induced rat mammary carcinomas are hormone-dependent adenocarcinomas histologically similar to human breast tumors (62,87,88).…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies (62,(83)(84)(85)(86) suggest that mammary carcinomas induced in Sprague-Dawley rats by 7,12-dimethylbenz(a)anthracene (DMBA) constitutes such a model. DMBA-induced rat mammary carcinomas are hormone-dependent adenocarcinomas histologically similar to human breast tumors (62,87,88). Tumor incidence is higher when the carcinogen is administered to nulliparous rats (62,83,89).…”

Section: Introductionmentioning

confidence: 99%

Molecular and Cellular Basis of the Mammary Gland Susceptibility to Carcinogenesis

Russo¹,

Tay²,

Ciocca³

et al. 1983

Environmental Health Perspectives

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Mammary carcinomas induced by the administration of 7,12-dimethylbenz(a)anthracene (DMBA) to young virgin rats arise from undifferentiated terminal ductal structures called terminal end buds (TEBs). TEBs that normally differentiate into alveolar buds (ABs) and lobules under the influence of DMBA develop intraductal proliferations which progress to carcinoma. The high susceptibility of the young virgin rat TEBs to neoplastic transformation is due to its large proliferative compartment, with cells cycling every 10 hr, and to a higher 3H-DMBA uptake. Progressive differentiation of TEBs into ABs and lobules or their regression to terminal ducts (TDs) is seen with aging. Complete differentiation of the gland is attained only through pregnancy and lactation. The greater differentiation of the gland is manifested as permanent structural changes, consisting in the disappearance of TEBs and in a diminution of the number of TDs due to their differentiation into ABs and lobules. This greater differentiation results in a diminished or total refractoriness of the gland to the carcinogen because ABs and lobules have a lower proliferative compartment and a longer cell cycle than TEBs and TDs. Cells of parous rats have both in vivo and in vitro a lower DMBA-DNA binding capacity, a lower DNA synthesis and a greater ability to repair DMBA damaged DNA than cells of young virgin rats. The more efficient DNA repair capacity of the parous rat mammary gland is demonstrated by the induction of unscheduled DNA synthesis and a removal of DMBA-DNA adducts.

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Pathogenesis of Mammary Carcinomas Induced in Rats by 7, 12-Dimethylbenz[a]anthracene2

Cited by 122 publications

References 0 publications

Impact of progesterone receptor on cell-fate decisions during mammary gland development

Impact of progesterone receptor on cell-fate decisions during mammary gland development

Mammary gland carcinogenesis by food‐derived heterocyclic amines: Metabolism and additional factors influencing carcinogenesis by 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)

Molecular and Cellular Basis of the Mammary Gland Susceptibility to Carcinogenesis

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