Analysis of chromosome aberrations, sister chromatid exchanges [SCE] and cell division kinetics in human lymphocytes exposed in vitro to new monophosphates of pyrimidine acyclonucleosides

Five newly synthesised monophosphates of two pyrimidine acyclonucleoside series, namely 1-N-[(2’-hydroxy)ethoxymethyl] and l-N-[(l’,3’-dihydroxy)- 2’-propoxymethyl] derivatives of 5- and 5,6-alkylated uracils were tested in vitro for chromosome aberrations and sister chromatid exchanges (SCE). Metaphase plates were obtained via microculture of human lymphocytes from heparinized peripheral blood. The compounds were tested in doses: 10, 20, 40, 80 and 150 µg per mL of culture. The tested compounds induced mainly chromatid gaps, less frequently chromosome gaps. A low number of mitoses with chromatid and chromosome breaks, acentric fragments, dicentric chromosomes and exchange figures were also observed. The tested compounds in doses: 40, 80 and 150 µg per mL, doubled or tripled the percentage of cells with chromatid gaps and chromosome gaps as compared to the control. The percentage o cells with aberrations (excluding gaps) induced by the tested compounds in all doses did not exceed 2%. The tested compounds induced a higher number of SCE per cell but less than double frequency as compared to the control. SCE frequencies and replication index (RI) values varied depending on the examined compounds. For the highest dose of the tested compounds (150 µg per mL) a significant decrease in RI values was observed for l-N-[(2’-hydroxy)ethoxymethyl]-5,6-tetramethyleneuracil monophosphate and for l-N-[(2’-hydroxy)ethoxymethyl]-5,6-dimethyluracil monophosphate. So far, the results have indicated potential clastogenicity of all the tested compounds except acycloguanosine monophosphate.