Evaluation of genotoxic and cytotoxic potential of thiola (N-2-mercaptopropionylglycine), a medicine used in the treatment of humans contaminated with mercury.
In Brazil, environmental contamination by mercury occurs mainly as a result of gold mining activities, especially in the Amazon region. In this area, human contamination results mainly from consumption of fish. Treatment of current symptoms of acute or chronic mercury contamination is normally carried out by increasing its excretion through metal scavenger compounds. In Japan, human contamination by mercury, which causes Minamata disease, has been successfully treated by the metal scavenger thiola (N-2 mercaptopropionylglycine). Its effects are based on its capacity to couple with the metal, facilitating its excretion. The possible clastogenic or anticlastogenic effect of thiola was evaluated by the in vivo micronucleus study in bone marrow erythrocytes of mice and also in human lymphocytes in vitro through chromosomal aberration analysis. In both experiments, different concentrations of thiola were used. Treatments with bleomycin (BLM), cyclophosphamide (CP), and also treatments combining these drugs with thiola were carried out with the purpose of studying the anticlastogenicity of thiola, considering its antioxidant properties. Thiola did not induce a significant increase in the micronucleus frequency in polychromatic erythrocytes of mice nor show any protective effect on the damage caused by bleomycin and cyclophosphamide in these cells. At a high dose, thiola showed a cytotoxic effect, significantly decreasing the relative proportion of polychromatic erythrocytes. In human lymphocytes, the tested drug did not increase the frequency of chromosomal aberration and also did not have any protective effect on the damage caused by BLM and CP.
Formigli
Lia M
LM
Departamento de Genética e Morfologia, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, Brazil.
Ferrari
Iris
I
Grisolia
Cesar K
CK
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology; D002869:Chromosome Aberrations; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008630:Mercury Poisoning / Q000188:drug therapy; D051379:Mice; D015162:Micronucleus Tests; D008625:Tiopronin / Q000494:pharmacology*
D001761:Bleomycin; D003520:Cyclophosphamide; D008625:Tiopronin