Thimerosal induces micronuclei in the cytochalasin B block micronucleus test with human lymphocytes.
Thimerosal is a widely used preservative in health care products, especially in vaccines. Due to possible adverse health effects, investigations on its metabolism and toxicity are urgently needed. An in vivo study on chronic toxicity of thimerosal in rats was inconclusive and reports on genotoxic effects in various in vitro systems were contradictory. Therefore, we reinvestigated thimerosal in the cytochalasin B block micronucleus test. Glutathione S-transferases were proposed to be involved in the detoxification of thimerosal or its decomposition products. Since the outcome of genotoxicity studies can be dependent on the metabolic competence of the cells used, we were additionally interested whether polymorphisms of glutathione S-transferases (GSTM1, GSTT1, or GSTP1) may influence the results of the micronucleus test with primary human lymphocytes. Blood samples of six healthy donors of different glutathione S-transferase genotypes were included in the study. At least two independent experiments were performed for each blood donor. Significant induction of micronuclei was seen at concentrations between 0.05-0.5 micro g/ml in 14 out of 16 experiments. Thus, genotoxic effects were seen even at concentrations which can occur at the injection site. Toxicity and toxicity-related elevation of micronuclei was seen at and above 0.6 micro g/ml thimerosal. Marked individual and intraindividual variations in the in vitro response to thimerosal among the different blood donors occurred. However, there was no association observed with any of the glutathione S-transferase polymorphism investigated. In conclusion, thimerosal is genotoxic in the cytochalasin B block micronucleus test with human lymphocytes. These data raise some concern on the widespread use of thimerosal.
Westphal
Götz A
GA
Department of Occupational Health, Georg-August-University Göttingen, Waldweg 37, 37073 Göttingen, Germany. gwestph@gwdg.de
Asgari
Soha
S
Schulz
Thomas G
TG
Bünger
Jürgen
J
Müller
Michael
M
Hallier
Ernst
E
D008841:Actin Cytoskeleton / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003571:Cytochalasin B / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D005838:Genotype; D005982:Glutathione Transferase / Q000097:blood / Q000145:classification / Q000235:genetics; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D015162:Micronucleus Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D011110:Polymorphism, Genetic; D011310:Preservatives, Pharmaceutical / Q000633:toxicity*; D013849:Thimerosal / Q000633:toxicity*
D009153:Mutagens; D011310:Preservatives, Pharmaceutical; D013849:Thimerosal; D003571:Cytochalasin B; D005982:Glutathione Transferase