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 deleter ious processes such as gene mutation, cellular transformation and cell death. Cellular response to DNA damage induced by hydrogen peroxide w as 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 ce lls treated with 1 mM hydrogen peroxide and then declined, but not to the control levels within 4 h. Interestingly, immunofluorescence stain ing of treated cells revealed that cytoplasmic hsp70 protein transloca ted transiently into the nucleus, which was most remarkable around 30 min after the addition of 1 mM hydrogen peroxide into the culture medi um. On the other hand, the induction of hsp70 gene mRNA was not signif icant 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 c leavage of DNA and nuclear translocation of hsp70 protein. These resul ts suggest that preexisting hsp70 protein translocated into the nucleu s to either protect chromatin DNA from further damage or to facilitate the repair of DNA damage in some unknown ways. (C) 1995 Academic Pres s, Inc.