The significance of selected biochemical markers in the characterization of putative initiated cell populations in rodent liver.

Biochemical 'markers' of neoplastic cells have been the subject of numerous investigations during the past several decades. Recently, studies from a number of laboratories have demonstrated that a very common biochemical marker for early 'preneoplastic' lesions occurring in several model systems of multistage carcinogenesis, especially hepatocarcinogenesis, is the enzyme, gamma-glutamyltranspeptidase (GGT). Despite the high frequency of this marker, especially in early hepatic lesions, an extensive degree of biochemical heterogeneity is evident when lesions are analyzed for the presence of multiple markers. Such markers have in the past been considered to be relatively stable. However, it is becoming increasingly apparent that environmental factors, drugs, diet, etc. may alter the phenotype of such lesions, especially in respect of GGT activity. Although various model systems have demonstrated different degrees of persistence of biochemically altered focal lesions induced during hepatocarcinogenesis, it is quite likely, but not yet proven, that the potential for the development of each focus remains in the tissue even on disappearance of the histochemical markers. Despite the relatively high frequency of the marker, GGT, in early focal lesions during hepatocarcinogenesis and the generally decreased level of xenobiotic metabolism in these lesions, no single marker, essential or critical for the neoplastic transformation in early or late lesions of hepatocarcinogenesis, has as yet been identified.