ARACHIDONIC-ACID METABOLISM BY NUCLEI OF A RETINOIC ACID - OR VITAMIN-D-3-DIFFERENTIATED HUMAN LEUKEMIA-CELL LINE HL-60

Arachidonic acid (AA) metabolism in nuclei of human pro-myelocytic leukemia (HL-60) cells was investigated during retinoic acid (RA)-induced granulocytic differentiation and 1 alpha,25 dihydroxy-vitamin D-3-induced monocytic differentiation. The whole control HL-60 cells and their nuclei hardly converted [1-C-14]-AA to any metabolites comigrating with authentic prostaglandins (PGs). On the other hand, RA-treated HL-60 cells acquired the ability to convert [1-C-14]-AA to PGE, predominantly and thromboxane B-2 (TXB(2)) to a small degree, whereas the nuclei of the differentiated cells acquired the ability to convert predominantly to TXB,. In contrast, 1 alpha,25-dihydroxy-vitamin D-3-treated HL-60 cells acquired the ability to convert [1-C-14]-AA to PGE(2), PGF(2 alpha), TXB(2) and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT), whereas the nuclei of the differentiated cells acquired the ability to convert to PGF(2 alpha), TXB(2) and HHT. The significance of the acquisition of cyclooxygenase and TX synthetase by the nucleus is unclear, but there may be a specific relationship between the specific PGs formed by the nuclear membrane and nuclear events during HL-60 cell differentiation.