Event:870

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Event Title

Cell Proliferation, Increase

Key Event Overview

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AOPs Including This Key Event

AOP Name Event Type Essentiality
Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors KE Strong

Taxonomic Applicability

Name Scientific Name Evidence Links
rat Rattus norvegicus Strong NCBI
mouse Mus musculus Moderate NCBI
human Homo sapiens Weak NCBI

Level of Biological Organization

Biological Organization
Cellular

How this Key Event works

Sustained atrophy/degeneration olfactory epithelium under the influence of a cytotoxic agent leads to adaptive tissue remodeling. Cell types unique to olfactory epithelium, e.g. olfactory neurons, sustentacular cells and Bowmans glands, are replaced by cell types comprising respiratory epithelium or squamous epithelium.

How it is Measured or Detected

Two common methods of measuring cell proliferation in vivo are the use of Bromodeoxyuridine (5-bromo-2'-deoxyuridine, BrdU) labeling[1], and Ki67 immunostaining[2]. BrdU is a synthetic analogue of the nucleoside Thymidine. BrDu is incorporated into DNA synthesized during the S1 phase of cell replication and is stable for long periods. Labeling of dividing cells by BrdU is accomplished by infusion, bolus injection, or implantation of osmotic pumps containing BrdU for a period of time sufficient to generate measureable numbers of labeled cells. Tissue sections are stained immunhistochemically with antibodies for BrdU and labeled cells are counted as dividing cells. Ki67 is a cellular marker of replication not found in quiescent cells[3]. Direct immunohistochemical staining of cells for protein Ki67 using antibodies is an alternative to the use of BrdU, with the benefit of not requiring a separate treatment (injection for pulse-labeling). Cells positive for Ki67 are counted as replicating cells. Replicating cell number is reported per unit tissue area or per cell nuclei[4].

Evidence Supporting Taxonomic Applicability

Cell proliferation is a central process supporting development, tissue homeostasis and carcinogenesis, each of which occur in all vertebrates. This key event has been observed nasal tissues of rats exposed to the chemical initiator vinyl acetate.

References

  1. Pera, Mattias and Detzer (1977). Methods for determining the proliferation kinetics of cells by means of 5-bromodeoxyuridine. Cell Tissue Kinet. 10: 255-264, Bogdanffy, Gladnick, Kegelman and Frame (1997). FOUR-WEEK INHALATION CELL PROLIFERATION STUDY OF THE EFFECTS OF VINYL ACETATE ON RAT NASAL EPITHELIUM. Inhalation Toxicology, Taylor & Francis. 9: 331-350
  2. Grogan, Lippman, Spier, Slymen, Rybski, Rangel, Richter and Miller (1988). Independent prognostic significance of a nuclear proliferation antigen in diffuse large cell lymphomas as determined by the monoclonal antibody Ki-67. Blood. 71: 1157-1160
  3. Grogan, Lippman, Spier, Slymen, Rybski, Rangel, Richter and Miller (1988). Independent prognostic significance of a nuclear proliferation antigen in diffuse large cell lymphomas as determined by the monoclonal antibody Ki-67. Blood. 71: 1157-1160
  4. Pera, Mattias and Detzer (1977). Methods for determining the proliferation kinetics of cells by means of 5-bromodeoxyuridine. Cell Tissue Kinet. 10: 255-264, Bogdanffy, Gladnick, Kegelman and Frame (1997). FOUR-WEEK INHALATION CELL PROLIFERATION STUDY OF THE EFFECTS OF VINYL ACETATE ON RAT NASAL EPITHELIUM. Inhalation Toxicology, Taylor & Francis. 9: 331-350