P6: Interesting paper about UV-induced apoptosis of thymocytes.

From: Dianne E. Godar, DEG@CDRH.FDA.GOV
Date: 11/25/97
Time: 11:02:35 PM
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This is a very interesting paper about UV-induced apoptosis of thymocytes. The authors found that UV can both induce and suppress apoptosis of thymocytes depending on the dose, i.e., induction occurs at low dose levels while inhibition occurs at high dose levels (> 20 J/m2). They also found that lipoxygenase, cyclooxygenase, PTK, phospholipase A2 and Ca2+ were not involved in UV-induced apoptosis of thymocytes. Furthermore, they also show that macromolecular inhibitors can induce apoptosis of thymocytes and inhibit UV-induced apoptosis (if you look carefully at the figures and compare the effects of these inhibitors on the shams and then the exposed cells). These results may at first appear to be contradictory, but we have shown that there are two mechanisms of apoptosis and only one,i.e., delayed or programmed cell death mechanism of apoptosis, is dependent on the synthesis of new proteins. I have a few questions for these authors concerning the materials and methods mostly. 1) What is the UV source and output characterisitics, i.e., is the primary emission in the UVA, UVB or UVC range? 2) What time post exposure were these measurements made? 3) How were the apoptotic cells quantified? Flow cytometry? (sorry if I missed this point) 4) What qualitative examinations were made to determine that the primary mode of cell death is apoptosis, and that necrosis did not play any role at higher dose levels? 5) It appears that the inhibitors are inducing apoptosis when no UV is present, could you comment about this observation? 6) Were the cell numbers the same in all the samples at the time of measurement? (If not then possibly these cells were lost during processing, underwent "secondary" necrosis, or primary necrosis. PI may miss these cells for they may lyse very rapidly and not display membrane damage at the time measured. And finally, what do you think is going on at the higher dose levels? Why do you think UV induces apoptosis at lower dose levels and inhibits it at higher levels? Is it possible that necrosis is taking over at the higher dose levels and the method of measurement is missing it? Or, maybe the cells are confused by the contradictory stimuli and one signal cancels out the other through some cross-talk mechanism, such as those observed in other immunological systems. Thank you for presenting a stimulating paper for discussion in this on-line conference. We will all learn from each others experiences and observations, and hopefully we will extend our understanding of this complex field. Who knows, we may even uncover the presence of yet another mode of cell death - God help us!

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