D-Ribose and deoxy-Dribose inhibited DNA, RNA, and protein synthesis in a wide variety of cells (dividing and nondividing, normal and neoplastic, freely floating and substrate adhering, human and murine) at concentrations at which other monosaccharides have little or no effect. Inhibition was irreversible and proportional to the sugar concentration and time of contact. However, the first effects were seen only after 24 hr of incubation and progressed slowly to cell death. Whether the two sugars share the same mechanisms of action is not known. In any case, they deeply derange metabolic processes in both dividing and nondividing cells. o 1985 Society for Experimental Biology and Medicine. 246
Quiescent human lymphocytes were damaged in two different ways, both producing toxic oxygen radicals: xanthine oxidase plus hypoxanthine (XOD/HYP), or gamma-rays. Under conditions where DNA synthesis was reduced to 10-20% of control, inhibitors of poly(ADP-ribosyl)polymerase (ADPRP, an enzyme that becomes activated in the presence of DNA strand breaks) allowed lymphocytes to recover completely when the damage was caused by XOD/HYP, but they did not affect DNA synthesis of irradiated cells. However, a protective effect of ADPRP inhibitors was observed with irradiated lymphocytes receiving doses greater than or equal to 50 Gy. Unscheduled DNA synthesis was Unscheduled DNA synthesis was significantly increased when lymphocytes were damaged by high radiation doses in the presence of ADPRP inhibitors. We suggest that ionizing radiation does not stimulate poly(ADP-ribose) synthesis in lymphocytes at doses that impair lymphocyte DNA synthesis by 80-90%, while ADPRP may be involved in the repair of DNA lesions occurring at higher radiation doses.
The enzyme poly(ADP-ribosyl)transferase (ADPRT) becomes activated soon after a mitogenic stimulus is applied to lymphocyte cultures. It has also been reported that ADPRT inhibitors prevent cell proliferation when added to cultures at the same time as the mitogen. While this has been ascribed to the need to seal physiologically present DNA strand breaks before cells enter S phase, the presence of DNA strand breaks in quiescent human lymphocytes has been recently questioned. We demonstrate here that non-toxic concentrations of ADPRT inhibitors do not affect lymphocyte blastization and proliferation, as measured by thymidine incorporation and cytofluorimetry. We therefore suggest that ADPRT activation is required for late functions which are not needed for cell cycle progression.
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