As to the clastogenic-, sister-chromatid exchange inducing-and cytotoxic activity of inosine triphosphate in cultures of human peripheral lymphocytes

Abstract The influence of commercial inosine triphosphate (ITP) on the chromosome aberration rate, the mitotic rate, sister-chromatid exchange (SCE) frequency, and the proportion of first (X1), second (X2) and third (X3) division metaphases was investigated in 72 h cultures of human peripheral lymphocytes. The blood donors had mild inactive arthrosis and a normal health check-up. All cultures of each volunteer were set-up simultaneously. In contrast to a previous report [Arch. Biochem. Biophys. 278 (1990) 238–244], it was demonstrated in two preliminary studies (number of subjects, n =5 each) that ITP at a final concentration of 100 μM does not induce chromosomal aberrations and, furthermore, that not ITP concentrations higher than 100 μM but ITP doses higher than 3.8 mM prohibit culture growth. Based on these results, cultures with a final ITP concentration of 3.6 mM (max.) and 1.8 mM (max./2) were compared with control cultures (number of subjects n =10; three males and seven females, mean age x =57.6 years). Whereas no increase in the chromosomal breakage rate was observed in cultures with an ITP concentration of 1.8 mM and only a marginally significant one ( P =0.048) for 3.6 mM ITP cultures, a highly significant induction of SCEs, not only at an ITP concentration of 3.6 mM ( P P P =0.027). The distribution of the number of SCEs per metaphase as well as the distribution of SCEs per chromosome correspond to the expected Poisson values. The investigation of the cytotoxic effect of the studied ITP concentrations revealed a highly significant reduction of the mitotic rate from 0 to 1.8 mM as well as from 1.8 to 3.6 mM in the aberration studies (all P values are equal to smallest possible one for a sample size of 10, namely, 0.002), and in the SCE studies there is a significant decrease in the X3 frequency when ITP is increased (0–1.8 mM: P =0.0061 and 1.8–3.6 mM: P P =0.22 and 1.8–3.6 mM ITP: P