Flow-cytometric analysis on cytotoxic effect of thimerosal, a preservative in vaccines, on lymphocytes dissociated from rat thymic glands.
There is a concern on the part of public health community that adverse health consequence by thimerosal, a preservative in vaccines for infants, may occur among infants during immunization schedule. Therefore, the cytotoxic action of thimerosal was examined on lymphocytes dissociated from thymic glands of young rats using a flow cytometer and respective fluorescent probes for monitoring changes in intracellular Ca2+ concentration ([Ca2+]i) and membrane potential, and for discriminating intact living cells, apoptotic living cells and dead cells. Incubation with thimerosal at 3 microM or more (up to 30 microM) for 60 min depolarized the membranes, associated with increasing the [Ca2+]i. Thimerosal at 30 microM induced an apoptotic change in membranes of almost all living cells. Furthermore, the prolonged incubation with 30 microM thimerosal induced a loss of membrane integrity, leading to cell death. Since the blood concentration of thimerosal after receiving vaccines is theoretically submicromolar, it may be unlikely that thimerosal affects lymphocytes of infants.
Ueha-Ishibashi
T
T
Laboratory of Cellular Signaling, Faculty of Integrated Arts and Sciences, The University of Tokushima, Minami-Jyosanjima 1-1, Tokushima 770-8502, Japan.
Oyama
Y
Y
Nakao
H
H
Umebayashi
C
C
Hirama
S
S
Sakai
Y
Y
Ishida
S
S
Okano
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry / Q000379:methods*; D007425:Intracellular Membranes / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011310:Preservatives, Pharmaceutical / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013849:Thimerosal / Q000633:toxicity*; D013950:Thymus Gland / Q000166:cytology; D014612:Vaccines / Q000009:adverse effects*
D011310:Preservatives, Pharmaceutical; D014612:Vaccines; D013849:Thimerosal; D002118:Calcium