The immunohistochemistry and in situ cDNA-mRNA hybridization of carbamyl phosphate synthetase I in enzyme-altered liver cells during carcinogenesis.

The changes of carbamyl phosphate synthetase I (CPS 1) in diethylnitrosamine-(DEN)-induced enzyme-altered liver cells were studied by means of immunohistochemical (PAP) and in situ cDNA-mRNA hybridization methods. The experimental rats were treated with DEN, 2-acetylaminofluorene (2-AAF) and 2/3 hepatectomy according to Solt-Farber's protocol and were further promoted by oral daily administration of 0.05% phenobarbital in drinking water. The results showed that the average number of lesions showing abnormal expression of CPS 1 was relatively constant over the course of the experiment (8 months), while the number of normally expressing lesions gradually decreased. The former lesions were also larger in volume than the latter ones. We conclude that in DEN-initiated lesions the abnormally expressed CPS 1 lesions may grow continuously, thus leading to the formation of larger nodules. We also suspect that some of these lesions have increased tendencies to develop into tumors.