Sequential ascending multiple-dose safety and pharmacokinetic study of oral lobucavir (BMS-180194) in asymptomatic volunteers seropositive for HIV and CMV: BG Petty, M Wachsman, MC Jordan, H Burgee, D DeHertogh, D Collins, RS Summerill, DA Jabs, JP Dunn, N Hellmann, B Kringstad, C Fletcher, L Smaldone, PS Lietman, MB Stewart. Division of Clinical Pharmacology, The Johns Hopkins University School of Medicine,

Abstract

The activities of three of the known DNA polymerases in HeLa cells have been determined in synchronized HeLa cells. Two of these enzymes increase their activity during the period of DNA synthesis (S-phase) which takes eight to ten hours of the total 24-hour cell cycle. The changes observed are: (a) the R-DNA (Fridlender et al., 1972) polymerase activity found in both the nucleus and cytoplasm increases just before and parallel with DNA synthesis. The enzyme level shows a maximum rise of 2.5-fold about two hours after the cells have entered the S-phase. (b) The large molecular weight D-DNA polymerase II (approx. 2×105) (Weissbach et al., 1971) in the cytoplasm increases slowly during the S-period and approaches maximal levels (twofold increase) after DNA synthesis has ceased. The D-DNA polymerase II activity found in the nucleus does not show a significant variation during this period. (c) The D-DNA polymerase I (Weissbach et al., 1971), a low molecular weight DNA polymerase (approx. 4×104) found in the nucleus, does not show any variation during S-phase.