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NAD(P)H:quinone oxidoreductase (NQO1) loss of function in Burkitt's lymphoma cell lines
Author(s) -
Brugè Francesca,
Virgili Samantha,
Cacciamani Tiziana,
Principi Federica,
Tiano Luca,
Littarru Gian Paolo
Publication year - 2008
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.5520320109
Subject(s) - raji cell , cell culture , oxidative stress , lymphoblast , cytosol , microbiology and biotechnology , nad+ kinase , chemistry , burkitt's lymphoma , biochemistry , cell , biology , enzyme , genetics
Two‐electron reduction of quinones catalyzed by NAD(P)H:quinone oxidoreductase (NQO1) protects cells against oxidative stress and toxic quinones. In fact, low level of NQO1 activity is often associated with increased risk of developing different types of tumours and with toxic effects linked to environmental quinones. In a previous report we analyzed the relationship between the oxidative stress induced by UV radiation and CoQ 10 content in Burkitt's lymphoma cell lines compared to HL‐60. The basal content of CoQ 10 in Raji cells was slightly higher compared to HL‐60. Moreover, after irradiation or ubiquinone supplementation in the medium, reduced CoQ 10 levels were higher in Raji and Daudi cells compared to HL‐60. In the present work, in order to inquire if NQO1 plays a role in the CoQ reducing capacity observed in the lymphoblastoid cell lines, we analyzed the transcription and translation products of this gene in Raji and Daudi cells, compared to cell lines possessing low and high NQO1 activity. The amount of transcripts of this gene in lymphoblastoid cells was comparable to that observed in HL‐60 cells (low activity), as well as the level of two alternatively spliced mRNAs; one of which is described for the first time in this work. From the genotype analysis of polymorphisms C609T and C465T we observed that HL‐60, Raji and Daudi cells were all heterozygous. Furthermore, NQO1 enzyme activity and protein synthesis in the cytosol of Raji and Daudi cells were undetectable. Therefore in Burkitt's lymphoma cell lines the NQO1 gene is not efficiently translated and this effect is not related to (C609T) polymorphism. Further studies will be necessary to find the enzyme responsible for CoQ 10 reducing activity observed in lymphoma cell lines. On the other hand, this result suggests a careful re‐evaluation of data concerning loss of NQO1 activity and polymorphisms in tumour cells.