Combined effects of bleomycin and X-rays on DNA synthesis in asynchronous Ehrlich ascites cells in suspension

Separate and combined effects of bleomycin and X-rays on rates of uptake of [14C]thymidine into Ehrlich ascites cells were assessed for extracellular drug concentrations of 12 micron (20 microgram/ml) and radiation doses of 2-5 krad. Rates of DNA synthesis were followed by monitoring the activity of the acid-insoluble portion of the asynchronous culture. The 14C activity of the acid-soluble pool was assessed in determining the rate of passage of 14C-TdR across the cell membrane. The results reveal that whilst the effects of each agent on TdR uptake rates are markedly different, they both inhibit DNA synthesis. Combined studies with both agents, 2-5 krad X-rays plus 20 microgram/ml bleomycin before, simultaneously or after exposure to X-rays, produced additive or less than additive effects on rates of incorporation of TdR into DNA. However, when the drug dose is split 2 X 10 microgram/ml before and after exposure to 2-5 krad X-rays, a synergistic effect on inhibition of DNA synthesis is observed.