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Polymorphism in nucleotide excision repair gene XPC correlates with bleomycin‐induced chromosomal aberrations
Author(s) -
Laczmanska Izabela,
Gil Justyna,
Karpinski Pawel,
Stembalska Agnieszka,
Trusewicz Alicja,
Pesz Karolina,
Ramsey David,
SchladeBartusiak Kamilla,
Blin Nikolaus,
Sasiadek Maria Malgorzata
Publication year - 2007
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.20333
Subject(s) - xrcc3 , nucleotide excision repair , xrcc1 , dna repair , biology , rad51 , ercc1 , genetics , dna damage , gene , base excision repair , dna mismatch repair , xeroderma pigmentosum , microbiology and biotechnology , single nucleotide polymorphism , dna , cancer research , genotype
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.