Accumulation of p53 protein in chemically induced oval cells during early stages of rodent hepatocarcinogenesis.
Up to now the possible involvement of p53 in rodent cancerogenesis has been based on results of the endpoint of chemically or virally induced carcinogenesis-tumors. To address the role of altered p53 expression in different stages of the multi-step process of rodent carcinogenesis in a systematic way we fed potent chemical carcinogens to male rats for 6, for 12 and for 6 weeks followed by a 6 week recovery period. Assessment of alterations of p53 expression was performed by immunoperoxidase staining with a polyclonal antiserum on frozen liver sections. Positive p53-immunostaining was localized to treatment-induced proliferating oval cells on liver sections of 21/21 2-acetylaminofluorene- (AAF) and 19/21 N-nitrosomorpholine (NNM)-treated rats irrespective of application scheme as well as to foci of hepatocytes in 1/21 NNM-treated animals and in 3/21 AAF-treated animals after 6 weeks of treatment only. The induction of oval cell proliferation by AAF was more pronounced than by NNM, and for NNM appeared to be dependent on application scheme, with a similar lower abundance of oval cells after a 6 week treatment with and without recovery as compared to a 12 week treatment. These results are discussed with respect to the role of p53 in human and rodent carcinogenesis on the one hand, and the disputed function of oval cells as facultative liver stem and tumour progenitor cells on the other.
Wirnitzer
U
U
Institute of Industrial Toxicology, Pharma Research Center, Bayer AG, Wuppertal, Germany.
Enzmann
H
H
Rosenbruch
M
M
Bomhard
E M
EM
D015073:2-Acetylaminofluorene; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression; D016158:Genes, p53; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009602:Nitrosamines; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000378:metabolism*
D009602:Nitrosamines; D016159:Tumor Suppressor Protein p53; C002741:N-nitrosomorpholine; D015073:2-Acetylaminofluorene