Naturally-occurring age-dependent glutathione S-transferase pi immunoreactive hepatocytes in aging female F344 rat liver as potential promotable targets for non-genotoxic carcinogens.
Naturally occurring basophilic foci (focal hepatocellular proliferative lesions) (FHPL) in the livers of aging female F344/NCr rats could not be promoted to grow or progress into tumors after phenobarbital (PB) exposure. Instead, PB induced new unique eosinophilic hepatocellular foci and adenomas much quicker in old rats than in young rats. We now report that these foci are immunoreactive for glutathione S-transferase pi (GSTP) and that they appear to arise from some naturally occurring single and double GSTP-reactive cells and foci which occur spontaneously in the liver of aging F344 rats in an age-related fashion. PB and other nongenotoxic chemicals may act as "carcinogens" by promoting the growth (clonal expansion) of some of these putative spontaneously-initiated cells and foci into tumors.
Ward
J M
JM
Tumor Pathology and Pathogenesis Section, National Cancer Institute, NCI-Frederick Cancer Research Facility, MD 21701.
Henneman
J R
JR
D000375:Aging; D000818:Animals; D001491:Basophils / Q000201:enzymology; D004804:Eosinophils / Q000201:enzymology; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000473:pathology; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values
D005982:Glutathione Transferase; D010634:Phenobarbital