Mitotic arrest and interphase inhibition induced by the pyrimidine sulfoxide NY 4138

Phase-specific cell-cycle inhibitory effects of the sulfoxide 5-bromo-2-(2-thienylmethyl)sulfinyl-pyrimidine (NY 4138) was studied on synchronized human NHIK 3025 cells cultivated in vitro. When added to exponentially growing cells, NY 4138 induced an accumulation of metaphases. The metaphase arrest was, however, not efficient immediately after addition of the compound. While a few telophases were still present 3 h after addition of 0.1 mM, no telophases were seen 6 h after addition. Most cells exposed to metaphase arrest by NY 4138 lost their ability to form colonies. We therefore characterize the metaphase arrest induced by this drug as irreversible. For concentrations above 0.5 mM phase specific cell cycle inhibition was also observed during interphase. Cells treated in G1 only were not delayed in G1 but were delayed in S and in G2. Cells treated in S only were also delayed in S, but to a smaller extent than the cells treated in G1 only. Cells treated with 0.1 mM NY 4138 for a period of 4 h in either G1 or in S showed no significant prolongation of the subsequent mitosis (i.e. the drug was in this case not present during mitosis). However, about 20% of the cells in this case divided to form 3 daughter cells of which 1 had a normal G1 DNA-content, 1 had 1/3 and 1 had 2/3 of a normal G1 DNA-content.