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We have assessed the intracellular metabolism of 2′‐deoxyadenosine in a human colon‐carcinoma cell line (LoVo), both in the absence and in the presence of deoxycoformycin, the powerful inhibitor of adenosine deaminase. 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 dependent on cell density. In the absence of deoxycoformycin, 2′‐deoxyadenosine 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 cleavage giving rise to adenine. The conversion of 2′‐deoxyadenosine to adenine might represent a protective device, emerging when the activity of adenosine deaminase is reduced or inhibited. There is much evidence to indicate that the enzyme catalyzing this process may be distinct from methylthioadenosine phosphorylase and S‐adenosyl homocysteine hydrolase, which are the enzymes reported to be responsible for the formation of adenine from 2′‐deoxyadenosine in mammals. Int. J. Cancer 75:713–720, 1998.© 1998 Wiley‐Liss, Inc.

The mutagenic activity of methylglyoxal (MG) was assayed in vitro in human lymphocytes [induction of chromosomal aberrations (CAs), sister chromatid exchanges (SCEs) and micronuclei] both in the presence and in the absence of metabolic activation (S9 mix). The Ames/microsome test was performed with the Salmonella typhimurium strains considered more responsive (TA102 and TA104). Positive results were obtained for all the genetic endpoints analysed. In human lymphocytes the activity of MG is decreased by the presence of S9 mix. In the in vivo studies, the metaphase analysis in the ileum and duodenum cells of mice treated per os with MG (400 and 600 mg/kg body wt) gave negative results for CA induction, while only a weak increase of SCE in duodenum cells at the higher dose was obtained. Dimethylhydrazine (25 mg/kg body wt), as positive control, was clearly active in inducing both CAs and SCEs in the same intestinal tissues.

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