Induction of polyploidy in human lymphocytes in vitro by excess adenine, but not by adenosine.
It is known that high levels of DNA precursors can be both clastogenic and mutagenic in cultured cell lines and in vivo. The purpose of the present study was to examine at an observational level the cytogenetic effects of adenine and adenosine in primary human cell cultures. Human peripheral blood lymphocytes from four donors were cultured and treated with a range of concentrations of adenine and adenosine. Although no increase in sister chromatid exchange (SCE) frequency was observed with either compound, there was a statistically significant, dose-related increase in the proportion of polyploid cells in cultures treated with adenine, but not in those treated with adenosine. Some of the polyploid metaphases found after adenine treatment contained diplochromosomes, suggesting that endoreduplication might have been involved in polyploid formation in these cells. It is concluded that a high level of adenine can cause genetic changes in human lymphocytes by interfering with mitosis, perhaps by disturbing the balance of DNA precursor pools.
Edwards
A J
AJ
BIBRA International, Surrey, England.
Anderson
D
D
Phillips
B J
BJ
D000225:Adenine / Q000633:toxicity*; D000241:Adenosine / Q000633:toxicity*; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008677:Metaphase / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects / Q000235:genetics; D011123:Polyploidy; D012854:Sister Chromatid Exchange / Q000187:drug effects / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects*
D000225:Adenine; D000241:Adenosine