DEOXYADENOSINE METABOLISM IN A HUMAN COLON-CARCINOMA CELL-LINE (LOVO)IN RELATION TO ITS CYTOTOXIC EFFECT IN COMBINATION WITH DEOXYCOFORMYCIN

We have assessed the intracellular metabolism of 2'-deoxyadenosine in a human colon-carcinoma cell line (LoVo), both in the absence and in t he presence of deoxycoformycin, the powerful inhibitor of adenosine de aminase. The combination of 2'-deoxyadenosine and deoxycoformycin has been reported to inhibit the growth of LoVo cells in culture. In this paper we demonstrate that the observed toxic effect is strictly depend ent on cell density. In the absence of deoxycoformycin, 2'-deoxyadenos ine is primarily deaminated to 2'-deoxyinosine and then converted into hypoxanthine. In the presence of the inhibitor, the deoxynucleoside, in addition to a phosphorylation process, undergoes phosphorolytic cle avage giving rise to adenine. The conversion of 2'-deoxyadenosine to a denine might represent a protective device, emerging when the activity of adenosine deaminase is reduced or inhibited. There is much evidenc e to indicate that the enzyme catalyzing this process may be distinct from methylthioadenosine phosphorylase and S-adenosyl homocysteine hyd rolase, which are the enzymes reported to be responsible for the forma tion of adenine from 2'-deoxyadenosine in mammals. (C) 1998 Wiley-Liss , Inc.