Lack of p53 induction in fish cells by model chemotherapeutics.
Although p53 has been extensively studied in mammalian models, relatively little is known about its specific function in lower vertebrates. It has long been assumed that p53 pathways characterized in mammals apply to other vertebrates as well. Fish provide a useful model for the study of environmental carcinogenesis, and populations of fish inhabiting highly polluted environments provide information on the etiology of pollutant-mediated cancer. In this study, we investigated p53 protein and apoptosis induction in PLHC-1 (desert topminnow hepatocellular carcinoma), RTL-W1 (rainbow trout normal liver), and primary rainbow trout hepatocytes exposed to model chemotherapeutics. All of the chemicals used in these studies have been demonstrated to increase p53 protein levels and induce apoptosis in mammalian cell lines. In contrast, PLHC-1 p53 protein was not induced in response to any model mammalian p53 inducers following 24 h exposures. Additionally, both trout cell types demonstrated this same lack of p53 induction upon exposure to model chemotherapeutic drugs. PLHC-1 cells demonstrated an induction of apoptosis as measured by caspase-3 activation following exposure to all of the chemotherapeutics tested. Our results suggest that fish p53 may be activated differently from that of their mammalian counterparts, and that important differences may exist between phyla in the function and regulation of p53 as well as other mechanisms involved in environmental carcinogenesis.
Rau Embry
M
M
Ecotoxicology Laboratory, Nicholas School of the Environment and Earth Sciences, Integrated Toxicology Program, Duke University, Durham, NC, USA. embry.michelle@epa.gov
Billiard
S M
SM
Di Giulio
R T
RT
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D023421:Models, Animal; D017686:Oncorhynchus mykiss; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000276:immunology
D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53