16/05/2018 1st Latin-American Congress of Clinical and Laboratorial Toxicology (TOXI-LATIN 2014)

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Title

TOXICOGENETIC EFFECT OF Ala16Val-SOD2 POLYMORPHISM IN METHYL MERCURY TOXICITY

Research Area

Genotoxicidade/Mutagenicidade

Presenter City/State

Algarve TD(1,2) SANTA MARIA/RIO GRANDE DO SUL

Other Authors

Lenz LS2; Cruz S2; Manica-Cattani MF2; Cruz IBM1,2

Institution

1 Programa de Pós-Graduação em Ciências Biológicas - Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal
de Santa Maria. 2 Laboratório de Biogenômica, Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal de Santa
Maria.

TOXICOGENETIC EFFECT OF Ala16Val-SOD2 POLYMORPHISM IN METHYL MERCURY TOXICITY

Introduction: Methylmercury (MeHg) is a well-known potential threat to human health owing to its capacity to cause systemic
toxicity that damages the body through neurotoxic effects; motor function impairment; immune, kidney, and cardiovascular
system dysfunction; and genotoxicity. The process responsible for triggering MeHg toxicity is incompletely understood and likely
involves metabolic alterations such as increased oxidative stress and inflammatory response. Conversely, gene polymorphism
studies related to oxidative stress triggered by Hg intoxication metabolism have focused mainly on glutathione (GSH)-related
enzymes. However, to define genetically susceptible risk groups completely, research is also needed on the genes/proteins
involved in the toxicodynamics - i.e, the mechanisms causing adverse effects in the organism. Of particular interest is the
manganese SOD enzyme (MnSOD), a primary antioxidant enzyme in the mitochondria that converts ROS into oxygen and H2O2.
The human MnSOD enzyme gene displays a diallelic polymorphism in the mitochondrial targeting sequence (MTS) in which
alanine 16 (GCT) is replaced with a valine (GTT) - the Ala16Val polymorphism (Ala16Val MnSOD) - this alteration reflects in the
enzyme structure and catalytic efficiency. The Ala16Val polymorphism results in 3 genotypes: AA, VV, and AV. We showed that
this polymorphism can modulate MeHg toxicity due to its capacity of product different amounts of H2O2 related to genotype (AA
> AV > VV) whereas VV presented a higher cellular viability when exposed to 2,5?M MeHg (Algarve et al., 2013). However it was
tested with one intermediate concentration of MeHg, but how many folds are the lethal doses between the Ala16Val-SOD2
genotypes? Methods: To test MeHg cytotoxicity in human periferical blood mononuclear cells (PBMC) of carriers previously
genotyped with different Ala16Val genotypes, we performed cell culture with and without MeHg (0; 0,1; 0,3; 1; 3; 10 and 30?M)
during 24h at 37°C in a humidified atmosphere. After this period, we analysed viability cell viability and free DNA in culture
medium through MTT and PicoGreen (PG) Assay. Results and Discussion: Preliminary data suggest that the difference is no too
high 1,43 fold higher MeHg concentration in VV genotype than AA, it means that to kill 50% of VV?s PBMC is necessary 11,31?M
when to kill the same ratio in AA genotype is necessary 7,9?M MeHg (p< 0,001). PG results showed that 0,3?M onward AA
genotype presented a higher free DNA in the culture medium (p< 0,0001) suggesting that AA presenting a higher cell lysis than
others genotypes. Conclusion and Acknowledgements: These results appoint to the toxicogenetic effect of MeHg when
considering the individual variation as Ala16Val-SOD2 polymorphism. We acknowledgement all people involved as volunteers,
CAPES and CNPq for financial support.

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