title: PTEN methylation involved in benzene-induced hematotoxicity.
abstract: It is well known that benzene is a hematotoxic carcinogen. PTEN promoter methylation is a representative example of transcriptional silencing of tumor suppressor genes. However, the effect of PTEN methylation on benzene-induced hematotoxicity has not yet been elucidated. In this study, the animal model of benzene hematotoxicity was successfully established. WBC significantly decreased in experimental groups (P < 0.01). Compared with the control group, the weight of rats increased slowly and even declined with increasing doses of benzene in the benzene-treated groups. An increase in the level of PTEN methylation was observed in the low dose group, and PTEN methylation level increased significantly in a dose-dependent manner. However, it was interesting that PTEN mRNA expression increased in the low dose group, but declined with increasing doses of benzene. The decrease of tumor suppressor function caused by PTEN methylation may be an important mechanism of benzene hematotoxicity. Furthermore, lymphoblast cell line F32 was incubated by benzene and then treated with 5-aza and TSA, alone or in combination. A dramatic decrease in the PTEN mRNA expression and a significant increase of PTEN methylation level in benzene-treated cells were also shown. PTEN mRNA expression was up regulated and PTEN methylation level was reduced by the epigenetic inhibitors, 5-aza and TSA. In conclusion, PTEN methylation is involved in benzene-induced hematotoxicity through suppressing PTEN mRNA expression.
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Bai
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Piye
authors.initials: P
authors.lastname: Niu
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. Electronic address: tianlin@ccmu.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. Electronic address: gaoai0980@163.com.
authors.forename: Ai
authors.initials: A
authors.lastname: Gao
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D001554:Benzene / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity; D045744:Cell Line, Tumor; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D015536:Down-Regulation; D044127:Epigenesis, Genetic / Q000187:drug effects; D016147:Genes, Tumor Suppressor / Q000187:drug effects; D006877:Hydroxamic Acids / Q000494:pharmacology; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D002273:Carcinogens; D006877:Hydroxamic Acids; D012333:RNA, Messenger; C012589:trichostatin A; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat; D001554:Benzene; D001374:Azacitidine
keywords: Benzene; Epigenetic modifications; Hematotoxicity; Methylation-specific PCR; PTEN