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, phosphorolytic activity acting on deoxyadenosine plays a maj or role in the resistance to the cytotoxic effect of the combination of deo xynucleoside with deoxycoformycin. In fact, the observed dependence of toxi city on cell density appears to be related to the metabolic conversion of d eoxyadenosine into adenine. The phosphorylation of the deoxynucleoside, whi ch represents the first step towards the formation of the cytotoxic agent d ATP, proceeds at a significantly lower rate as compared to the phosphorolys is of deoxyadenosine. The analysis of the levels of deoxyadenosine and its derivatives in the incubation media reveals that the rates of disappearance of deoxyadenosine and of formation of adenine increase in concert with the reduction of the effect on cell survival. J. Cell. Biochem. 80:241-247, 20 00. (C) 2000 Wiley-Liss, Inc.