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Enhanced sensitivity to DNA damage induced by cooking oil fumes in human OGG1 deficient cells
Author(s) -
Wu Mei,
Che Wangjun,
Zhang Zunzhen
Publication year - 2008
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.20381
Subject(s) - a549 cell , dna damage , comet assay , dna repair , cell culture , genotoxicity , microbiology and biotechnology , cell , chemistry , viability assay , biology , dna , biochemistry , genetics , toxicity , organic chemistry
Cooking oil fumes (COFs) have been implicated as an important nonsmoking risk factor of lung cancer in Chinese women. However, the molecular mechanism of COFs‐induced carcinogenicity remains unknown. To understand the molecular basis underlying COFs‐induced cytotoxicity and genotoxicity as well as the roles of hOGG1 in the repair of COFs‐induced DNA damage, a human lung cancer cell line with hOGG1 deficiency, A549‐R was established by using a ribozyme gene targeting technique that specifically knockdowned hOGG1 in A549 lung adenocarcinoma cells. MTT and comet assays were employed to examine cell viability and DNA damage/repair, respectively, in A549‐R and A549 cell lines treated with COF condensate (COFC). RT‐PCR and Western blot results showed that the expression of hOGG1 in A549‐R cell line was significantly decreased compared with that in A549 cell line. The concentration of COFC that inhibited cell growth by 50% (the IC 50 ) in the A549‐R cell line was much lower than that in the A549 cell line, and more COFC‐induced DNA damage was detected in the A549‐R cell line. The time course study of DNA repair demonstrated delayed repair kinetics in the A549‐R cell line, suggesting a decreased cellular damage repair capacity. Our results showed that hOGG1 deficiency enhanced cellular sensitivity to DNA damage caused by COFC. The results further indicate that hOGG1 plays an important role in repairing COF‐induced DNA damage. Our study suggests that COFs may lead to DNA damage that is subjected to hOGG1 ‐mediated repair pathways, and oxidative DNA damage may be involved in COF‐induced carcinogenesis. Environ. Mol. Mutagen., 2008. © 2008 Wiley‐Liss, Inc.