Standardized assessment of cell proliferation: the approach of the RITA-CEPA working group

Exp Toxicol Pathol. 2005 Nov;57(2):91-103. doi: 10.1016/j.etp.2005.06.002. Epub 2005 Aug 10.

Abstract

Since 1985, quantitative data on cell proliferation increasingly form an integral part in the risk assessment of many pharmaceutical, chemical, and agrochemical compounds. Technical guides for the conduct of cell proliferation studies are not readily available. The detection of cell proliferation relies almost exclusively on immunohistochemistry, which is rarely standardized between laboratories. Against this background pathologists formed the RITA-CEPA working group with the aim of elaborating standard guides for the conduct of cell proliferation studies. We present here, as examples, the general BrdU guide as well as the organ-specific guides for hepatocytes, thyroid gland follicular cells, and renal tubular epithelial cells in the rat. Today, RITA-CEPA has available guides for BrdU cell proliferation studies in 20 organs as well as for studies with PCNA as proliferation marker and for apoptosis studies with the TUNEL technique. The relevant information from more than 500 selected publications is organized in a database structure to make it easily traceable. New hardware and software used for image analysis are being assessed and are included in the information exchange practiced in the CEPA working group. Further fields of major relevance for cell proliferation studies, such as statistics and the validation of image analysis equipment in a GLP environment are investigated. A guide on the use of statistics in cell proliferation studies is in preparation. CEPA-group members meet regularly to exchange information. They use the electronic database for planning and interpretation of cell proliferation studies. CEPA will continue with the preparation of organ guides and expand the series for other proliferation markers, e.g. Ki-67. It promotes standardization of techniques applied in proliferation studies, especially immunohistochemistry and image analysis. Members of the CEPA-group have access to a comprehensive and steadily increasing knowledge base on all aspects of cell proliferation. Membership of the CEPA group is open for all industrial organizations who develop chemical, agrochemical, or pharmaceutical products.

Publication types

  • Review

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism*
  • Cell Proliferation*
  • Histocytological Preparation Techniques / standards*
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Kidney / cytology
  • Liver / cytology
  • Organ Specificity
  • Rats
  • Staining and Labeling
  • Thyroid Gland / cytology

Substances

  • Bromodeoxyuridine