Responses of mouse liver to dechlorane plus exposure by integrative transcriptomic and metabonomic studies.
Dechlorane plus (DP), a chlorinated flame retardant, has been widely detected in different environmental matrices and biota. However, toxicity data for DP have seldom been reported. In the present study, we investigated hepatic oxidative stress, DNA damage, and transcriptomic and metabonomic responses of male mice administered 500 mg/kg, 2000 mg/kg, and 5000 mg/kg of DP by gavage for 10 days. The results showed that DP exposure increased the level of superoxide dismutase (SOD) and 8-hydroxy-2-deoxyguanosine (8-OHdG). The microarray-based transcriptomic results demonstrated that DP exposure led to significant alteration of gene expression involved in carbohydrate, lipid, nucleotide, and energy metabolism, as well as signal transduction processes. The NMR-based metabonomic analyses corroborated these results showing changes of metabolites associated with the above altered mechanisms. Our results demonstrate that an oral exposure to DP can induce hepatic oxidative damage and perturbations of metabolism and signal transduction. These observations provide novel insight into toxicological effects and mechanisms of action of DP at the transcriptomic and metabonomic levels.
State Key Lab of Pollutant Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, P.R. China. bwu@nju.edu.cn
Bing
B
Wu
Su
S
Liu
Xuechao
X
Guo
Yan
Y
Zhang
Xuxiang
X
Zhang
Mei
M
Li
Shupei
S
Cheng
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D050260:Carbohydrate Metabolism / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005411:Flame Retardants / Q000008:administration & dosage / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006843:Hydrocarbons, Chlorinated / Q000008:administration & dosage / Q000633:toxicity*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011083:Polycyclic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism; D018675:Toxicity Tests
D005411:Flame Retardants; D006843:Hydrocarbons, Chlorinated; D011083:Polycyclic Compounds; C526360:dechlorane plus; D000080242:8-Hydroxy-2'-Deoxyguanosine; D013482:Superoxide Dismutase; D003849:Deoxyguanosine