Enhanced sensitivity to DNA damage induced by cooking oil fumes in human OGG1 deficient cells.
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 IC50) 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.
Wu
Mei
M
Department of Environmental Health, West China School of Public Health, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Che
Wangjun
W
Zhang
Zunzhen
Z
D000393:Air Pollutants / Q000633:toxicity*; D045744:Cell Line, Tumor; D020552:Comet Assay; D003296:Cooking; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D005229:Fatty Acids, Monounsaturated; D006801:Humans; D010938:Plant Oils; D012333:RNA, Messenger / Q000378:metabolism; D000074262:Rapeseed Oil
D000393:Air Pollutants; D005229:Fatty Acids, Monounsaturated; D010938:Plant Oils; D012333:RNA, Messenger; D000074262:Rapeseed Oil; D004247:DNA; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human