The 1996 Veylien Henderson Award of the Society of Toxicology of Canada. Current concepts: neutrophils and the activation of carcinogens in the breast and other organs

1998 ◽  
Vol 76 (7-8) ◽  
pp. 693-700 ◽  
Author(s):  
P David Josephy ◽  
Brenda L Coomber
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Chemical Carcinogenesis ◽  
Reactive Species ◽  
Epithelial Tissue ◽  
Chemical Carcinogens ◽  
Tissue Inflammation ◽  
Epithelial Tissues

Many chemical carcinogens target epithelial tissues, but the biological and biochemical bases of carcinogen specificity remain largely unknown. Focusing on the mammary gland, we discuss the concept that neutrophils metabolize carcinogens to reactive species that damage adjacent epithelial cells. This mechanism may help to explain why epithelial cells are sensitive targets for chemical carcinogenesis, despite their limited bioactivation capacity.Key words: carcinogenesis, neutrophil, bioactivation, peroxidase, epithelial tissue, inflammation.

scholarly journals Chemerin Regulates Epithelial Barrier Function of Mammary Glands in Dairy Cows

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3194
Author(s):  
Yutaka Suzuki ◽  
Sachi Chiba ◽  
Koki Nishihara ◽  
Keiichi Nakajima ◽  
Akihiko Hagino ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Dairy Cows ◽  
Barrier Function ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Epithelial Barrier ◽  
Epithelial Tissue ◽  
Epithelial Barrier Function

Epithelial barrier function in the mammary gland acts as a forefront of the defense mechanism against mastitis, which is widespread and a major disorder in dairy production. Chemerin is a chemoattractant protein with potent antimicrobial ability, but its role in the mammary gland remains unelucidated. The aim of this study was to determine the function of chemerin in mammary epithelial tissue of dairy cows in lactation or dry-off periods. Mammary epithelial cells produced chemerin protein, and secreted chemerin was detected in milk samples. Chemerin treatment promoted the proliferation of cultured bovine mammary epithelial cells and protected the integrity of the epithelial cell layer from hydrogen peroxide (H2O2)-induced damage. Meanwhile, chemerin levels were higher in mammary tissue with mastitis. Tumor necrosis factor alpha (TNF-α) strongly upregulated the expression of the chemerin-coding gene (RARRES2) in mammary epithelial cells. Therefore, chemerin was suggested to support mammary epithelial cell growth and epithelial barrier function and to be regulated by inflammatory stimuli. Our results may indicate chemerin as a novel therapeutic target for diseases in the bovine mammary gland.

scholarly journals Non-autonomous induction of epithelial lineage infidelity and hyperplasia by DNA damage

2019 ◽  
Author(s):  
Lindsey Seldin ◽  
Ian G. Macara
Keyword(s):  
Dna Damage ◽  
Stem Cell ◽  
Mammary Gland ◽  
Hair Follicle ◽  
Epithelial Tissue ◽  
Cell Hyperplasia ◽  
Stromal Fibroblasts ◽  
Epithelial Tissues ◽  
Lineage Infidelity ◽  
Genotoxic Agents

ABSTRACTSeveral epithelial tissues contain stem cell reserves to replenish cells lost during normal homeostasis or upon injury. However, how epithelial tissues respond to distinct types of damage, and how stem cell plasticity and proliferation are regulated in these contexts, remain poorly understood. Here, we reveal that genotoxic agents, but not mechanical damage, induce hyperplasia and lineage infidelity in three related epithelial tissues: the mammary gland, interfollicular epidermis and hair follicle. Furthermore, DNA damage also promotes stromal proliferation. In the mammary gland, we find that DNA damage activates multipotency within the myoepithelial population and hyper-proliferation of their luminal progeny, resulting in tissue disorganization. Additionally, in epidermal and hair follicle epithelia, DNA damage induces basal cell hyperplasia with the formation of abnormal, multi-layered K14+/K10+ cells. This behavior does not involve apoptosis or immunity, and is epithelial cell non-autonomous; stromal fibroblasts are both necessary and sufficient to induce the epithelial response. Thus, genotoxic agents that are used chemotherapeutically to promote cancer cell death can have the opposite effect on wild-type epithelial tissue, paradoxically promoting hyperplasia and inducing both stemness and lineage infidelity.

scholarly journals Epigenetically regulated digital signaling defines epithelial innate immunity at the tissue level

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Helen R. Clark ◽  
Connor McKenney ◽  
Nathan M. Livingston ◽  
Ariel Gershman ◽  
Seema Sajjan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Single Molecule ◽  
Single Cells ◽  
Population Level ◽  
Tissue Level ◽  
Fine Tuning ◽  
Epithelial Tissue ◽  
Epigenetic Switch ◽  
Epithelial Tissues ◽  
Molecular Patterns

AbstractTo prevent damage to the host or its commensal microbiota, epithelial tissues must match the intensity of the immune response to the severity of a biological threat. Toll-like receptors allow epithelial cells to identify microbe associated molecular patterns. However, the mechanisms that mitigate biological noise in single cells to ensure quantitatively appropriate responses remain unclear. Here we address this question using single cell and single molecule approaches in mammary epithelial cells and primary organoids. We find that epithelial tissues respond to bacterial microbe associated molecular patterns by activating a subset of cells in an all-or-nothing (i.e. digital) manner. The maximum fraction of responsive cells is regulated by a bimodal epigenetic switch that licenses the TLR2 promoter for transcription across multiple generations. This mechanism confers a flexible memory of inflammatory events as well as unique spatio-temporal control of epithelial tissue-level immune responses. We propose that epigenetic licensing in individual cells allows for long-term, quantitative fine-tuning of population-level responses.

scholarly journals 42 Quantifying mammary growth and proliferative effects of estradiol in Holstein heifer calves

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 42-43
Author(s):  
Nicole R Hardy ◽  
Kellie Enger ◽  
Benjamin Enger
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Cellular Proliferation ◽  
Corn Oil ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Epithelial Tissue ◽  
Proliferating Cells ◽  
Tissue Area ◽  
The Right

Abstract Growth of the bovine mammary gland is influenced by estradiol during a heifer’s life. The objective of this study was to determine the effect of estradiol administration on two different mammary parenchymal tissue regions and quantify the response in cellular proliferation between different estradiol treatments and regions. Treatments were administered daily during the 12 days prior to euthanasia at 82 days of age. Holstein heifer calves (n = 12) were divided amongst 3 treatments, control (n = 4, CON), short term (n = 4, SHORT), and long term (n = 4, LONG). CON calves were administered corn oil injections while SHORT calves received 9 injections of corn oil followed by 3 injections of estradiol; LONG calves received 12 injections of estradiol. BrdU was administered 2 hours prior to harvest to label proliferating mammary epithelial cells. Mammary parenchyma was dissected from the right rear gland and separated into two regions, center and edge parenchyma, for further examination. Tissues were examined using brightfield microscopy and fluorescent immunohistochemistry. LONG calves had a greater percentage (P < 0.05) of epithelial tissue area (34.0% ± 1.51) than CON (21.4% ± 1.5) and SHORT (23.0% ± 1.51) calves, and a lower stromal tissue area percentage (63.6% vs 73.9% and 74.0% ± 2.10, respectively; P < 0.05). There was a treatment by region interaction in the cellular proliferation. LONG calves had a greater percentage of proliferating epithelial cells than CON calves in the center (P < 0.05) and edge (P < 0.05) parenchymal regions, and a greater percentage of proliferating cells in the center parenchyma than SHORT calves (P < 0.05). These results indicate that duration of estradiol administration elicits different effects on mammary growth and that mammary epithelial cell proliferation is specific to mammary gland region.

HAZARD: An Expert System for Risk Assessment of Environmental Chemicals

1987 ◽  
Vol 26 (01) ◽  
pp. 13-23 ◽  
Author(s):  
H. W. Gottinger
Keyword(s):  
Expert System ◽  
Structural Information ◽  
Chemical Carcinogenesis ◽  
Structural Features ◽  
Environmental Chemicals ◽  
Chemical Carcinogens ◽  
Carcinogenic Activity ◽  
Current State ◽  
Structure Activity ◽  
Carcinogenic Potential

AbstractThe purpose of this paper is to report on an expert system in design that screens for potential hazards from environmental chemicals on the basis of structure-activity relationships in the study of chemical carcinogenesis, particularly with respect to analyzing the current state of known structural information about chemical carcinogens and predicting the possible carcinogenicity of untested chemicals. The structure-activity tree serves as an index of known chemical structure features associated with carcinogenic activity. The basic units of the tree are the principal recognized classes of chemical carcinogens that are subdivided into subclasses known as nodes according to specific structural features that may reflect differences in carcinogenic potential among chemicals in the class. An analysis of a computerized data base of known carcinogens (knowledge base) is proposed using the structure-activity tree in order to test the validity of the tree as a classification scheme (inference engine).

scholarly journals Mammary gland adipocytes in lactation cycle, obesity and breast cancer

2021 ◽  
Author(s):  
Georgia Colleluori ◽  
Jessica Perugini ◽  
Giorgio Barbatelli ◽  
Saverio Cinti
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Close Association ◽  
Critical Role ◽  
Exocrine Gland ◽  
Plastic Properties ◽  
Lactation Cycle ◽  
Gland Development

AbstractThe mammary gland (MG) is an exocrine gland present in female mammals responsible for the production and secretion of milk during the process of lactation. It is mainly composed by epithelial cells and adipocytes. Among the features that make the MG unique there are 1) its highly plastic properties displayed during pregnancy, lactation and involution (all steps belonging to the lactation cycle) and 2) its requirement to grow in close association with adipocytes which are absolutely necessary to ensure MG’s proper development at puberty and remodeling during the lactation cycle. Although MG adipocytes play such a critical role for the gland development, most of the studies have focused on its epithelial component only, leaving the role of the neighboring adipocytes largely unexplored. In this review we aim to describe evidences regarding MG’s adipocytes role and properties in physiologic conditions (gland development and lactation cycle), obesity and breast cancer, emphasizing the existing gaps in the literature which deserve further investigation.

scholarly journals Effects of bone morphogenetic proteins on epithelial repair

2021 ◽  
pp. 153537022110281
Author(s):  
Yu Hou ◽  
Yu-Xi He ◽  
Jia-Hao Zhang ◽  
Shu-Rong Wang ◽  
Yan Zhang
Keyword(s):  
Growth Factors ◽  
Epithelial Cells ◽  
Bone Morphogenetic Proteins ◽  
Epithelial Tissue ◽  
Epithelial Repair ◽  
Multiple Functions ◽  
Epithelial Damage ◽  
Damage Repair ◽  
And Migration ◽  
Proliferation And Migration

Epithelial tissue has important functions such as protection, secretion, and sensation. Epithelial damage is involved in various pathological processes. Bone morphogenetic proteins (BMPs) are a class of growth factors with multiple functions. They play important roles in epithelial cells, including in differentiation, proliferation, and migration during the repair of the epithelium. This article reviews the functions and mechanisms of the most profoundly studied BMPs in the process of epithelial damage repair and their clinical significance.

In vitro and in vivo pathologic effects of Vibrio parahaemolyticus on human epithelial cells

1984 ◽  
Vol 30 (3) ◽  
pp. 381-388 ◽  
Author(s):  
B. R. Merrell ◽  
R. I. Walker ◽  
S. W. Joseph
Keyword(s):  
Epithelial Cells ◽  
Epithelial Tissue ◽  
Ileal Mucosa ◽  
Cytotoxic Factor ◽  
Culture Cells ◽  
Vibrio Parahemolyticus ◽  
Buccal Epithelial Cells ◽  
Culture Supernate

The initial interaction and adherence of Vibrio parahemolyticus to epithelial tissue culture cells, human buccal epithelial cells, and the ileal mucosa of mice were studied. Using scanning electron microscopy, adherent bacteria were observed only on degenerating human embryonic intestinal, HeLa, and buccal cells; healthy normal cells were devoid of bacteria. Sheared V. parahaemolyticus, i.e., lacking flagella, did not adhere to either normal or degenerating tissue cells. Neither ultraviolet-inactivated organisms nor cell-free culture supernate affected the epithelial cells. Similar findings were observed on the mucosa of the ileum in mice inoculated with V. parahaemolyticus. It appears that V. parahaemolyticus possesses a cytotoxic factor which alters epithelial cells. This factor appears to be closely associated with viable organisms and may be a functional element in the adherence process of flagellated V. parahaemolyticus to mammalian epithelial cells.

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