Hunter syndrome: Long-term idursulfase treatment does not protect patients against DNA oxidation and cytogenetic damage

•MPS II patients present higher levels of DNA oxidation than control individuals.•They show an increase in micronuclei frequency, which indicates cytogenetic damage.•Treatment with enzyme replacement therapy does not protect them from these damages. Mucopolysaccharidosis type II (MPS II or Hunter sy...

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Published in:	Mutation research. Genetic toxicology and environmental mutagenesis Vol. 835; pp. 21 - 24
Main Authors:	Diaz Jacques, Carlos Eduardo, de Souza, Heryk M., Sperotto, Nathalia D.M., Veríssimo, Rodrigo M., da Rosa, Helen T., Moura, Dinara J., Saffi, Jenifer, Giugliani, Roberto, Vargas, Carmen Regla
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01-11-2018
Subjects:	Comet assay Enzyme replacement therapy Genotoxicity Micronucleus Mucopolysaccharidosis type II Mucopolysaccharidosis type II MN MPS II DI ERT Genotoxicity GAG Comet assay BUD 8-OHG BMCyt Enzyme replacement therapy Micronucleus 8-OHGn LSD 8-OHdG
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Summary:	•MPS II patients present higher levels of DNA oxidation than control individuals.•They show an increase in micronuclei frequency, which indicates cytogenetic damage.•Treatment with enzyme replacement therapy does not protect them from these damages. Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is an inborn error of metabolism characterized by the accumulation of glycosaminoglycans (GAG) in lysosomes. Enzyme replacement therapy (ERT) can reduce GAG storage, ameliorate symptoms, and slow disease progression. Oxidative damages may contribute to the MPS II pathophysiology, and treatment with ERT might reduce the effects of oxidative stress. We evaluated levels of DNA damage (including oxidative damage) and chromosome damage in leukocytes of long-term-treated MPS II patients, by applying the buccal micronucleus cytome assay. We observed that, despite long-term ERT, MPS II patients had higher levels of DNA damage and higher frequencies of micronuclei and nuclear buds than did control. These genetic damages are presumably due to oxidation: we also observed increased levels of oxidized guanine species in MPS II patients. Therapy adjuvant to ERT should be considered, in order to decrease oxidative damage and cytogenetic alterations.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1383-5718 1879-3592
DOI:	10.1016/j.mrgentox.2018.08.013