As to the clastogenic-, sister-chromatid exchange inducing-and cytotoxic activity of inosine triphosphate in cultures of human peripheral lymphocytes.
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 72h 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 microM does not induce chromosomal aberrations and, furthermore, that not ITP concentrations higher than 100 microM but ITP doses higher than 3.8mM prohibit culture growth. Based on these results, cultures with a final ITP concentration of 3.6mM (max.) and 1.8mM (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 1.8mM and only a marginally significant one (P=0.048) for 3.6mM ITP cultures, a highly significant induction of SCEs, not only at an ITP concentration of 3.6mM (P<0.0001) but also at 1.8mM (P<0.0001) was seen. The increase in the SCE frequency was not linear, but steeper from 0 to 1.8mM than from 1.8 to 3.6mM. Nevertheless, the difference between 1.8 and 3.6mM cultures was significant (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 1.8mM as well as from 1.8 to 3.6mM 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 (0-1.8mM: P=0.0061 and 1.8-3.6mM: P<0.0001). The proportion of X1 within all X1 and X2 metaphases changes significantly only at the second dose step (0-1.8mM ITP: P=0.22 and 1.8-3.6mM ITP: P<0.0001). The results are discussed.
Vormittag
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W
Department of Internal Medicine III, Division of Rheumatology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. walter_vormittag@hotmail.com
Brannath
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W
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D007293:Inosine Triphosphate / Q000008:administration & dosage / Q000633:toxicity*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D008938:Mitosis / Q000187:drug effects; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D009153:Mutagens; D007293:Inosine Triphosphate