Taxol protects the microtubules of concanavalin A-activated lymphocytes from disassembly by methylmercury, but DNA synthesis is still inhibited.
We have shown previously that there is a good correlation between the degree of microtubule disassembly by methylmercury (MeHg) and the extent of inhibition of DNA replication in Concanavalin A (Con A)-stimulated mouse splenic lymphocytes. The purpose of this study was to determine if these two events are causally related and to examine the effects of MeHg-induced microtubule disassembly on earlier events of the stimulation process. We show that early steps constituting the activation pathway, such as the Con A-induced increase in Ca2+ influx and the expression of interleukin 2 receptor, are not inhibited by concentrations of MeHg that disassemble microtubules. RNA synthesis is not affected by short-term (3 h) treatment with MeHg, but longer treatment (24 h) inhibits RNA synthesis. In contrast, DNA synthesis is effectively inhibited by a 3-h treatment with MeHg. In lymphocytes treated with taxol, microtubules are not disassembled by MeHg; however, the inhibition of RNA and DNA synthesis persists. We conclude that the inhibition of nucleic acid synthesis by MeHg is not causally related to MeHg-induced microtubule disassembly.
Roy
C
C
Department of Biology, University of Ottawa, Ontario, Canada.
Prasad
K V
KV
Reuhl
K R
KR
Little
J E
JE
Valentine
B K
BK
Brown
D L
DL
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003208:Concanavalin A / Q000276:immunology*; D004261:DNA Replication / Q000187:drug effects; D007700:Kinetics; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008767:Methylmercury Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008870:Microtubules / Q000187:drug effects*; D017239:Paclitaxel; D012313:RNA / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000378:metabolism
D000470:Alkaloids; D008767:Methylmercury Compounds; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; D012313:RNA; D017239:Paclitaxel; D002118:Calcium