Endonuclease activity and induction of DNA fragmentation in human myelogenous leukemic cell lines

When four human myelogenous leukemic cell lines (HL-60, ML-1, U-937, THP-1) were exposed to either ascorbic acid, hydrogen peroxide, etoposide, tumor necrosis factor, hyperthermia or UV irradiation, their growth inhibition and oligonucleosome-size DNA fragmentation were induced. Non-myelogenous leukemic cell lines (MOLT-4, K-562) were similarly sensitive to ascorbic acid and hydrogen peroxide, but relatively resistant to etoposide, TNF, hyperthermia and UV irradiation. Furthermore, these treatments except for UV irradiation, did not induce any apparent DNA fragmentation in MOLT-4 and K-562 cells. An autodigestion experiment revealed that all of these six cell lines contained divalent cation-independent endonuclease activity as a major endonuclease. The ability of this endonuclease to produce oligonucleosome-size DNA fragmentation was stimulated at acidic, but not at neutral pH. Since this enzyme activity was not detected in the lysosomal enzyme-free nuclei, prepared from all six cell lines, the cytoplasmic localization of this enzyme was suggested. The results suggest that the endonuclease activity might be differently regulated between myelogenous and non-myelogenous leukemic cell lines.