IMPORTANCE OF AND APPROACHES TO QUANTIFICATION OF HEPATOCYTE APOPTOSIS

Abnormal regulation of the life cycle of cells is a key feature of neo plasia. The net increase and growth of initiated cells, preneoplastic lesions, and tumors is highly dependent on rates of both cell prolifer ation and cell death. Studies of mechanisms involved in regulation of cell death and the development of methods to detect dying and dead cel ls thus appear to be as important as measurements of cell proliferatio n in understanding the growth of both normal, preneoplastic and neopla stic lesions. This article describes apoptosis in the mouse liver and its potential role in liver carcinogenesis. Quantitation of hepatocyte apoptosis is a emerging and evolving research area that will require evaluations as thoroughly as those performed with cell proliferation i n order to understand all the variables that might influence its occur rence, measurement, and interpretations. Utilizing available data, var ious methodologies for identifying hepatocyte apoptosis are presented and compared. Aspects important for the quantitation of apoptosis in l iver are emphasized. Accurate quantitation of apoptosis, in conjunctio n with proliferation measurements, is critical for investigations of t he mechanisms of chemically induced carcinogenesis and the development of assays for growth alterations and can be applied to biologically b ased cancer models.