Human trisomy 21 fibroblasts rescue methotrexate toxic effect after treatment with 5-methyl-tetrahydrofolate and 5-formyl-tetrahydrofolate.

摘要: Trisomy 21 causes Down syndrome (DS), the most common human genetic disorder and leading cause of intellectual disability. The alteration one-carbon metabolism was described as possible metabolic disability development in subjects with DS. One biochemical pathways involved group transfer is folate cycle. cytotoxic drug methotrexate (MTX) a folic acid (FA) analogue which inhibits activity dihydrofolate reductase enzyme cells are more sensitive to MTX effect than euploid cells, 1986 Jerome Lejeune Coll. demonstrated that twice toxic trisomy lymphocytes control cells. In present work, rescue on toxicity mediated by FA some its derivatives, tetrahydrofolate (THF), 5-formyl-THF, 5-methyl-THF, both normal skin fibroblast evaluated. A statistically significant obtained their combination, administered together MTX. conclusion, cell lines showed good response effects 5-formyl-THF 5-methyl-THF almost lines.