STRESS PROTEIN EXPRESSION IN RAT-LIVER DURING TUMOR 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 (HSP s), HSPs protect cells against irreversible protein damage and are inv olved in adaptive responses to stress stimuli. Some HSPs are overexpre ssed in neoplasias, possibly contributing to the increased drug tolera nce often observed in such lesions, We have studied HSP expression in two experimental rat hepatocarcinogenesis models. Our aim was to clari fy whether they are involved in stress adaptation in hepatocytes durin g carcinogen exposure, and whether HSPs may contribute to xenobiotic r esistance in preneoplastic lesions, The complete carcinogen 2-acetylam inofluorene (AAF) was used in a continuous feeding protocol, and in th e resistant hepatocyte model where the growth of diethylnitrosamine in itiated 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 mediatin g an adaptive response to stress caused by reactive AAF metabolites. E nzyme altered preneoplastic foci were not found to overexpress HSPs. T hus, HSP induction does not seem to be a general mechanism underlying the increased stress tolerance observed in such lesions.