Bile duct-bound growth of precursor cells of preneoplastic foci inducible in the initiation stage of rat chemical hepatocarcinogenesis by 2-acetylaminofluorene.

Background: We previously detected precursor cell populations of preneoplastic foci, GST-P+/GGT(-) and GST-P+/GGT(+) minifoci, in rat liver in the initiation stage of chemical hepatocarcinogenesis, where GST-P and GGT represent glutathione S-transferase P-form and gamma-glutamyltranspeptidase, respectively. Methods: Sprague-Dawley male rats were fed a basal diet containing 2-acetylaminofluorene (0.02%) over 16 weeks. Precursor cells were detected by our sensitive staining method for GGT activity and immunocytochemical staining for GST-P. Results: GST-P+/GGT(-) single cells were overproduced maximally in the animal liver after the 6 weeks followed by a gradual growth of GST-P+/GGT(-) and GST-P+/GGT(+) minifoci, which were bound to bile ducts and ductules. GGT was expressed within GST-P+ minifoci gradually with time forming GGT(+) lane-like structures. The bile duct binding and lane-like structure formation were prominent especially when minifoci-bearing rats were subjected to two-thirds partial hepatectomy. Conclusions: A variety of precursor minifoci were noted to be selectively bound to bile ducts and ductules in rat liver, which may be of physiologic significance in excretion of carcinogens during initiation.