The anti-inflammatory activities of six benzoxazinoids isolated from roots of Coix lachryma-jobi var. ma-yuen and structurally related synthetic materials were investigated by measurement of their inhibition of histamine release from rat mast cells stimulated with concanavalin A (Con A) and sensitized with immunoglobulin E (reagin). Because the inhibition data for either Con A or IgE with these compounds were comparable, Con A can be used for rapid first-stage screening of active compounds. Four glycosides out of the eleven compounds investigated were not active. Other results showed that the free hydroxyl group at the 2-position in the benzoxazinone skeleton is important for the expression of inhibitory activity.
SummaryAfter an exposure to ionising radiation, cells can quickly repair damage to their genomes; however, a few unrepairable DNA doublestrand breaks (DSBs) emerge in the nucleus in a prolonged culture and perpetuate as long as the culture continues. These DSBs may be retained forever in cells such as non-dividing ageing tissues, which are resistant to apoptosis. We show that such unrepairable DSBs, which had been advocated by the classical target theory as the 'radiation hit', could account for permanent growth arrest and premature senescence. The unrepairable DSBs build up with repeated irradiation, which accounts for an accumulated dose. Because these DSBs tend to be paired, we propose that the untethered and 'torn-off' molecular structures at the broken ends of the DNA result in an alteration of chromatin structure, which protects the ends of the DNA from genomic catastrophe. Such biochemical responses are important for cell survival but may cause gradual tissue malfunction, which could lead to the late effects of radiation exposure. Thus, understanding the biology of unrepairable damage will provide new insights into the long-term effects of radiation.
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