کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10900129 | 1084544 | 2008 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Genetic variation of Aflatoxin B1 aldehyde reductase genes (AFAR) in human tumour cells
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
AFAR genes play a key role in the detoxification of the carcinogen Aflatoxin B1 (AFB1). In the rat, Afar1 induction can prevent AFB1-induced liver cancer. It has been proposed that AFAR enzymes can metabolise endogenous diketones and dialdehydes that may be cytotoxic and/or genotoxic. Furthermore, human AFAR1 catalyses the rate limiting step in the synthesis of the neuromodulator γ-hydroxybutyrate (GHB) and was found elevated in neurodegenerative diseases such as Alzheimer's and dementia with Lewy bodies (DLB). The human AFAR gene family maps to a genomic region in 1p36 of frequent hemizygous deletions in various human cancers. To investigate, if genetic variation of AFAR1 and AFAR2 exists that may alter protein detoxification capabilities and confer susceptibility to cancer, we have analysed a spectrum of human tumours and tumour cell lines for genetic heterogeneity. From 110 DNA samples, we identified nine different amino acid changes; two were in AFAR1 and seven in AFAR2. In AFAR1, we found genetic variation in the proposed substrate-binding amino acid 113, encoding Ala113 or Thr113. An AFAR2 variant had a Glu55 substituted by Lys55 at a position that is conserved among many aldo-keto reductases. This polarity change may have an effect on the proposed substrate binding amino acids nearby (Met47, Tyr48, Asp50). Further population analyses and functional studies of the nine variants detected may show if these variants are disease-related.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 272, Issue 1, 8 December 2008, Pages 160-166
Journal: Cancer Letters - Volume 272, Issue 1, 8 December 2008, Pages 160-166
نویسندگان
Christian Praml, Wolfgang Schulz, Andreas Claas, Jan Mollenhauer, Annemarie Poustka, Rolf Ackermann, Manfred Schwab, Kai-Oliver Henrich,