Unit Length as the Denominator for Quantitation of Cell Proliferation in Nasal Epithelia

Abstract

Cell proliferation data, generally based on a labeling index (LI), provide a valuable endpoint for assessment of toxic and potentially carcinogenic responses in laboratory animals. Measurement of the LI is time consuming because of the large number of cells that need to be counted to determine the denominator. In respiratory mucosa, the total cell count of the surface epithelia may be altered in response to treatment, either through cell loss or increases in cell number (e.g., hyperplasia). As an alternative to the more conventional LI, the present studies were carried out to assess the value of expressing cell proliferation in nasal epithelia as a unit length labeling index (ULLI), defined as labeled cells per mm of basement membrane. Rats were exposed by inhalation to formaldehyde or methyl bromide, and changes in cell proliferation were determined in the respiratory and olfactory epithelia, respectively, using both total cell count and basement membrane length as denominators. Total cell counts were clearly influenced by treatment, while basement membrane length was not. Both methods revealed similar treatment-induced effects on cell proliferation, and in fact were highly correlated (R ≥ 0.92, p < 0.001). It was concluded that the ULLI method provides an effective alternative to total cell counts and the LI method. This approach is not influenced by alterations in the total cell population, and has the benefit of being less labor intensive than LI determinations.