B. Lindeman et al., STRESS PROTEIN EXPRESSION IN RAT-LIVER DURING TUMOR PROMOTION - INDUCTION OF HEAT-SHOCK-PROTEIN-27 IN HEPATOCYTES EXPOSED TO 2-ACETYLAMINOFLUORENE, Carcinogenesis (New York. Print), 19(9), 1998, pp. 1559-1563
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.