POSSIBLE CORRELATION BETWEEN DNA-DAMAGE INDUCED BY HYDROGEN-PEROXIDE AND TRANSLOCATION OF HEAT-SHOCK-70 PROTEIN INTO THE NUCLEUS

Oxygen radicals have been implicated as the causative agent in deleterious processes such as gene mutation, cellular transformation and cell death. Cellular response to DNA damage induced by hydrogen peroxide was examined in human amniotic cultured cells (WISH). The content of 8-hydroxydeoxyguanosine in nuclear DNA increased during the early period of exposure to hydrogen peroxide, that is, it peaked at 1 h in the cells treated with 1 mM hydrogen peroxide and then declined, but not to the control levels within 4 h. Interestingly, immunofluorescence staining of treated cells revealed that cytoplasmic hsp70 protein translocated transiently into the nucleus, which was most remarkable around 30 min after the addition of 1 mM hydrogen peroxide into the culture medium. On the other hand, the induction of hsp70 gene mRNA was not significant during the early period of treatment by 0.5 mM hydrogen peroxide and was occurred after 5 h. DNA damage induced by Adriamycin further supported the possible correlation between hydroxyl radical-mediated cleavage of DNA and nuclear translocation of hsp70 protein. These results suggest that preexisting hsp70 protein translocated into the nucleus to either protect chromatin DNA from further damage or to facilitate the repair of DNA damage in some unknown ways. (C) 1995 Academic Press, Inc.