Cytokeratin expression during AFB1-induced carcinogenesis.
The early stages of the carcinogenic process induced by aflatoxin B1 (AFB1) in rat liver during 24 weeks of feeding and the resulting tumours have been studied with respect to cytokeratin (CK) expression. A previously uncharacterized monoclonal antibody, MRCTU/J1, has been shown to recognize rat CK18 and together with antibodies against human CK8, 18 and 19, has been used to examine the possible lineage of tumour cells and also to identify the altered foci that might be most relevant to tumorigenesis. Results suggested that AFB1-induced transformation in liver may occur in more than one cell type, since tumours with the normal hepatocyte CK pattern and those with bile duct or oval cell CK phenotype were identified. Additionally, hepatocytes with a bile duct CK phenotype appeared during the early stages of carcinogenesis. The in vivo pattern of CK expression also appeared to be maintained in one normal and one hepatoma-derived cell line. Overexpression of CKs (particularly of CK19) was a much more selective marker for altered foci, compared to gamma-glutamyltranspeptidase, and was more consistently expressed at high levels in tumours, suggesting that it might be a more reliable way of identifying those cells involved in the transformation process.
MRC Toxicology Unit, Carshalton, Surrey, UK.
J A
JA
Green
P
P
Carthew
E
E
Heuillet
J L
JL
Simpson
M M
MM
Manson
D016604:Aflatoxin B1; D000348:Aflatoxins; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000032:analysis / Q000139:chemically induced; D003429:Cross Reactions / Q000276:immunology; D003599:Cytoskeleton / Q000032:analysis*; D007382:Intermediate Filaments / Q000032:analysis*; D007633:Keratins / Q000032:analysis*; D008099:Liver / Q000032:analysis*; D008114:Liver Neoplasms, Experimental / Q000032:analysis* / Q000139:chemically induced / Q000276:immunology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured / Q000032:analysis / Q000276:immunology
D000348:Aflatoxins; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D007633:Keratins; D016604:Aflatoxin B1