Polymorphism in nucleotide excision repair gene XPC correlates with bleomycin-induced chromosomal aberrations

Chromosomal aberrations (CAs) are important genetic alterations in the development and progression of the majority of human cancers. The frequency with which such alterations occur depends to a large extent on polymorphisms of DNA-repair genes and in genes coding for xenobiotic metabolizing enzymes,...

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Published in:Environmental and molecular mutagenesis 2007-10, Vol.48 (8), p.666-671
Main Authors: Laczmanska, Izabela, Gil, Justyna, Karpinski, Pawel, Stembalska, Agnieszka, Trusewicz, Alicja, Pesz, Karolina, Ramsey, David, Schlade-Bartusiak, Kamilla, Blin, Nikolaus, Sasiadek, Maria Malgorzata
Format: Article
Language:English
Subjects:
Biological and medical sciences
Bleomycin - toxicity
chromosomal aberrations (CA)
Chromosome Aberrations
DNA Repair - genetics
DNA-repair genes polymorphisms
Female
Fundamental and applied biological sciences. Psychology
Genetics of eukaryotes. Biological and molecular evolution
Humans
Linkage Disequilibrium
Male
Medical sciences
Polymorphism, Genetic
single nucleotide polymorphism (SNP)
Toxicology
xenobiotic metabolic genes polymorphisms (XME)
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Summary:Chromosomal aberrations (CAs) are important genetic alterations in the development and progression of the majority of human cancers. The frequency with which such alterations occur depends to a large extent on polymorphisms of DNA-repair genes and in genes coding for xenobiotic metabolizing enzymes, which are involved in the processes of activation and inactivation of xenobiotics. The frequency of bleomycin (BLM)-induced CAs is an indirect measure of the effectiveness of DNA repair mechanisms, and a predictor of environment-related risk of cancer. Our study was conducted on the human peripheral blood lymphocytes of 82 healthy volunteers. The aim of the study was to elucidate whether the frequency of BLM-induced CAs is correlated with polymorphisms of selected genes involved in different mechanisms of DNA repair such as: XRCC1 [base excision repair]; XPA, XPC, XPG, XPD, XPF, ERCC1 [nucleotide excision repair], NBS1, RAD51, XRCC2, XRCC3, RAD51, and BRCA1 [homologous recombination], as well as in genes encoding xenobiotic metabolizing enzymes, such as CYP1A, CYP2E1, NAT2, GSTT1, and EPHX (mEH). Our study indicated that, of the polymorphisms studied, only XPC (exon 15 and intron 11) is associated with BLM-induced CAs, suggesting a role of the NER pathway in the repair of BLM-induced chromosomal aberrations. Environ. Mol. Mutagen., 2007. © 2007 Wiley-Liss, Inc.
ISSN:0893-6692
1098-2280
DOI:10.1002/em.20333