Immunohistochemically demonstrated suppressed expression of tryptophan oxygenase, a marker for liver differentiation, within putative preneoplastic rat liver lesions.

The behaviour of rat liver putative preneoplastic lesions with respect to the enzyme tryptophan oxygenase (TO), a liver-specific differentiation marker, and a possible growth-related marker, glucose-6-phosphate dehydrogenase (G6PD) was investigated during and after their induction by diethylnitrosamine initiation and subsequent 'selection pressure'. Using specific antibodies to rat liver TO and G6PD and the avidin-biotin complex method for immunohistochemical staining it was demonstrated that all of the nodular lesions showing increased expression of G6PD during the induction phase were also negative or deficient in TO enzyme protein. With the onset of 'phenotypic instability' or loss of marker enzymes, a gradual return to normal expression of TO activity was evident. Administration of dexamethasone and L-tryptophan 11 weeks after cessation of carcinogen treatment allowed differentiation between morphologically altered, apparently persisting lesions in which no, or little, enzyme induction was apparent and instable lesions showing a strong increase in levels of TO protein. Thus, persisting nodular lesions share a common lack of response to normal homeostatic physiological control.