[Etoposide-induced deoxyribonucleic acid (DNA) damage and its effects on nucleotide pools in murine leukemia L1210...

The effect of etoposide-induced deoxyribonucleic acid (DNA) damage and its effect on nucleotide pools were examined in murine leukemia L1210 cells. Etoposide (15 mg/kg) was administered intraperitoneally on the third day after peritoneal inoculation of 1 x 10(6) L1210 cells. The dosage of etoposide produced 175% of the increase of lifespan as described previously. Strand breaks in DNA occurred within 10 min after i.p. injection, but as the time interval between injection and removal of the cells from the mice was elongated to 1 and 3 h, the continuous repairing of DNA was observed. At 6 h after the injection, the maximum concentration of DNA was located in the vicinity of that of control. In our previous study, ara-C was most effective when given at 3 to 6 h after the administration of etoposide. The sensitivity to ara-C might increase during the repairing period from the etoposide-induced DNA damage. All four dNTPs increased progressively within 6 h up to 3-fold of control. The changes in rNTPs were similar, but the degree of the changes was smaller than that of dNTPs. These changes in dNTPs and rNTPs would be an important factor for the combination to determine the antitumor effect of etoposide and nucleoside analogues.