Role of the phosphorolysis of deoxyadenosine in the cytotoxic effect of the combination of deoxyadenosine and deoxycoformycin on a human colon carcinoma cell line (LoVo)

In LoVo cells, phosphorolyti c activit y actin g on deoxyadenosine plays a major role in the resistanc e to the cytotoxic effect of the combination of deoxynucleoside with deoxycoformycin. In fact, the observed dependence of toxicity on cell densit y appear s to be related to the metabolic conversion of deoxyadenosine into adenine . The phosphorylatio n of the deoxynucleoside, which represent s the firs t step toward s the formatio n of the cytotoxic agent dATP , proceeds at a significantl y lower rat e as compared to the phosphorolysi s of deoxyadenosine. The analysi s of the levels of deoxyadenosine and its derivative s in the incubation media reveals tha t the rates of disappearanc e of deoxyadenosineand of formatio n of adenin eincreas ein concert with thereduction of theeffect on cell survival.