Inhibition of DNA and RNA synthesis in lymphocyte cultures by rod outer segments and its counteraction by vitamin E and other antioxidants.

Bovine rod outer segments (ROS) specifically stimulate DNA synthesis in lymphocyte cultures from guinea pigs preimmunized with ROS. At doses above 10 microgram/ml protein, however, preparations of ROS inhibit DNA and RNA synthesis by the sensitized lymphocytes or by normal lymphocytes reacting to mitogens. The inhibtion of RNA synthesis becomes apparent after 24 hr of incubation, whereas little effect was detected after 6 hr. Of the lymphocytes tested, those from mouse and guinea pig spleen were the most susceptible to the effects of ROS, whereas were completely refractory to tested doses of ROS. Bovine retina homogenates were moderately inhibitory, whereas the corresponding cytosol fractions had no detectable effect. Intact ROS were less inhibitory than the disrupted ones, but only minimal amounts of inhibitory activity leaked from disrupted ROS during incubation. Two ROS components, retinoids and docosahexaenoic acid, were also inhibitory to the lymphocytes. The effects of ROS, retinoids, or docosahexaenoic acid were counteracted by antioxidants, with alpha-tocopherol (vitamin E) providing the best protection against ROS. These data thus show lymphocyte cultures to be useful for studying the damaging potential of ROS components and the essential role of antioxidants in protecting the retinal tissues.