Stress protein expression in rat liver during tumour promotion: induction of heat-shock protein 27 in hepatocytes exposed to 2-acetylaminofluorene.
Exposure of cells to a variety of stresses such as heat, radiation and xenobiotics leads to increased expression of heat-shock proteins (HSPs). HSPs protect cells against irreversible protein damage and are involved in adaptive responses to stress stimuli. Some HSPs are overexpressed in neoplasias, possibly contributing to the increased drug tolerance often observed in such lesions. We have studied HSP expression in two experimental rat hepatocarcinogenesis models. Our aim was to clarify whether they are involved in stress adaptation in hepatocytes during carcinogen exposure, and whether HSPs may contribute to xenobiotic resistance in preneoplastic lesions. The complete carcinogen 2-acetylaminofluorene (AAF) was used in a continuous feeding protocol, and in the resistant hepatocyte model where the growth of diethylnitrosamine initiated lesions is efficiently promoted. Of the HSPs tested, only heat-shock protein 27 (hsp27) was induced during continuous AAF exposure. After 4 weeks of feeding AAF, increased hsp27 expression was noted in hepatocytes in perivenous areas of the liver lobule, possibly mediating an adaptive response to stress caused by reactive AAF metabolites. Enzyme altered preneoplastic foci were not found to overexpress HSPs. Thus, HSP induction does not seem to be a general mechanism underlying the increased stress tolerance observed in such lesions.
Institute of Pathology, The National Hospital, University of Oslo, Norway. birgitte.lindeman@labmed.uio.no
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Lindeman
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Skarpen
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Huitfeldt
D015073:2-Acetylaminofluorene / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D006360:Heat-Shock Proteins; D015073:2-Acetylaminofluorene