To investigate the genotoxicity and reveal the potential toxicological mechanisms of Hexabromocyclododecane (HBCD), human breast cells HBL-100 were exposed to a sequence of HBCD concentrations (0, 5, 10, and 50 mg/L) for 24 h. With a series of zymology and molecular biology methods, we found that HBCD induced dose-dependent oxidative stress on HBL-100 DNA. As revealed in qRT-PCR, activated prognostic factor ATM down-regulated tumor suppressor gene BRCA1 and prompted DNA repair genes hOGG1 and hMTH1 expression in lower concentrations of HBCD (< 10 mg/L). However, DNA repair were inhibited as well as cell proliferation rate by higher concentrations of HBCD (50 mg/L). The results inferred that the genotoxicity of HBCD was dose-dependent and related to DNA repair pathway.
Breast Neoplasms ; chemically induced ; genetics ; Cell Line, Tumor ; DNA Damage ; Dose-Response Relationship, Drug ; Environmental Pollutants ; toxicity ; Female ; Flame Retardants ; toxicity ; Humans ; Hydrocarbons, Brominated ; toxicity ; Oxidative Stress ; Random Allocation

Humans ; Hydrocarbons, Brominated ; toxicity ; Occupational Exposure ; standards

OBJECTIVETo study the effects of 1-bromopropane (1-BP) on liver and kidney functions of exposed workers.

METHODSOccupational health situation in three 1-BP plants was investigated. Fifty-four workers from the 1-BP manufacturing line were chose to be contact group, while 42 workers from non-1-BP manufacturing line as control group. All workers underwent questionnaire survey, liver function test as well as kidney function test.

RESULTWorking years has no impact on liver and kidney functions of workers from contact group. Compared with the control, liver and kidney functions test of the two groups showed no statistical difference either.

CONCLUSIONThe present investigation doesn't prove any impact of occupational 1-BP exposure on worker's liver and kidney functions.

Humans ; Hydrocarbons, Brominated ; toxicity ; Kidney ; drug effects ; Liver ; drug effects ; Occupational Exposure ; adverse effects

Electrophysiological Phenomena ; drug effects ; Humans ; Hydrocarbons, Brominated ; toxicity ; Occupational Exposure ; adverse effects

Blood Glucose ; Humans ; Hydrocarbons, Brominated ; toxicity ; Occupational Exposure ; adverse effects

Cardiovascular System ; drug effects ; Humans ; Hydrocarbons, Brominated ; toxicity ; Occupational Exposure ; adverse effects

Hematologic Tests ; Humans ; Hydrocarbons, Brominated ; toxicity ; Occupational Exposure ; adverse effects

OBJECTIVETo investigate the changes in the expression of DNA methyltransferases (DNMTs) and activities of histone acetyltransferase (HAT) and histone deacetylase (HDAC) in the testis of male rats exposed to bromopropanes (BPs).

METHODSTwenty-seven male rats were randomly divided into three groups to be intraperitoneally injected with 1-BP,2-BP, or corn oil (as a control) for two weeks. The sperm count and morphology in the epididymis were evaluated. The mRNA expression of DNMT1, DNMT3a, and DNMT3b and activities of HAT and HDAC in the testis were measured by quantitative real-time PCR and ELISA.

RESULTSCompared with the control group, the BP exposure groups showed significant decreased absolute and relative sperm counts; the proportion of tailless sperm increased in the 1-BP exposure group, while the proportion of sperm with abnormal heads increased in the 2-BP exposure group. The 2-BP exposure group had significantly lower mRNA expression of DNMT1, DNMT3a, and DNMT3b than the control group (P < 0.05). There were no significant differences in the activities of HAT and HDAC between the control group and 1-BP exposure group; the 2-BP exposure group showed significantly higher HAT activity than the control group (P < 0.05), but no significant difference was found in HDAC activity between them.

CONCLUSIONExposure to 2-BP might induce abnormal DNA methylation and histone acetylation, and epigenetic regulation might play an important role in the reproductive toxicity of 2-BP.

Acetylation ; drug effects ; Animals ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases ; metabolism ; DNA Methylation ; drug effects ; Histones ; metabolism ; Hydrocarbons, Brominated ; toxicity ; Male ; Rats ; Rats, Sprague-Dawley ; Sperm Count ; Testis ; drug effects ; metabolism

OBJECTIVETo investigate the protective effects of docosahexaenoic acid (DHA) and nervonic acid (NA) on the learning and memory abilities in rats exposed to 1-bromopropane (1-BP) and their action mechanisms.

METHODSForty male Wistar rats (specific pathogen-free) were randomly divided into 4 groups (n = 10 for each), i.e., solvent control group, 1-BP (800 mg/kg) group, NA (150 mg/kg) + 1-BP (800 mg/kg) group, and DHA (500 mg/kg) + 1-BP (800 mg/kg) group. The rats were given respective test substances by gavage for 7 d. The Morris water maze (MWM) test was performed from days 8 to 12 to evaluate the rats' learning and memory abilities. After MWM test, rats were sacrificed in the next day, and cerebral cortex was quickly dissected and homogenized in an ice bath. The supernatant of the obtained homogenate was collected to measure the content of glutathione (GSH) and malondialdehyde (MDA) and the activities of glutathione reductase (GR) and γ-glutamate cysteine ligase (γ-GCL).

RESULTSThe MWM spatial navigation test showed that the 1-BP group had significantly longer escape latency and significantly longer total swimming distance compared with the control group (P<0.05), while the DHA+1-BP group had significant decreases in escape latency and total swimming distance compared with the 1-BP group (P<0.05). The spatial probe test showed that the number of platform crossings was significantly greater in the DHA+1-BP group and NA+1-BP group than in the 1-BP group (P<0.05); compared with the control group, the 1-BP group had a significantly lower ratio of time spent in the zone around the platform to total time (P < 0.05), and the ratio was significantly higher in the DHA+1-BP group than in the 1-BP group (P < 0.05). Compared with the control group, the 1-BP group had a 18.1% decrease in GSH content, and DHA could significantly reverse 1-BP-induced decrease in GSH content (P < 0.05). Compared with the 1-BP group, the DHA+1-BP group and NA+1-BP group had significantly decreased MDA content (P < 0.05), the DHA+1-BP group had significantly increased GR activity (P < 0.05), and the NA+1-BP group had significantly increased γ-GCL activity (P < 0.05).

CONCLUSIONThe rats exposed to 1-BP have oxidative stress in the brain and impaired cognitive function. DHA and NA can reduce 1-BP-induced cognitive function impairment in rats, possibly by increasing the activities of GR and γ-GCL and the content of GSH in the brain.

Animals ; Behavior, Animal ; Brain ; drug effects ; Docosahexaenoic Acids ; pharmacology ; Fatty Acids, Monounsaturated ; pharmacology ; Glutamate-Cysteine Ligase ; metabolism ; Glutathione ; metabolism ; Glutathione Reductase ; metabolism ; Hydrocarbons, Brominated ; toxicity ; Male ; Malondialdehyde ; metabolism ; Maze Learning ; drug effects ; Memory ; drug effects ; Oxidative Stress ; Rats ; Rats, Wistar

OBJECTIVETo observe the peripheral neurotoxicity of 1-bromopropane (1-BP) by developing an animal model of peripheral neuropathy through oral administration of 1-BP.

METHODSForty male Wistar rats were randomly and equally divided into low-dose group (200 mg/kg), medium-dose group (400 mg/kg), high-dose group (800 mg/kg), and control group. The rats in the low-dose, medium-dose, and high-dose groups were orally given 1-BP (dissolved in corn oil), while the rats in the control group were orally given an equal volume of corn oil. The oral administration (0.2 ml/100 g BW) was performed once per day, 5 days per week, for 16 consecutive weeks. Neurobehavioral indices including gait score, hindlimb grip strength, and hindlimb landing foot splay were recorded periodically. Hematological and biochemical parameters were also measured during and after 1-BP exposure.

RESULTSThe gait scores were significantly higher in the high-dose group (after 8 ∼ 16 weeks of 1-BP exposure), medium-dose group (after 14 ∼ 16 weeks of 1-BP exposure), and low-dose group (after 15 ∼ 16 weeks of 1-BP exposure) than in the control group (P < 0.05, P < 0.01). Compared with the control group, the high-dose group showed significantly decreased hindlimb grip strength after 9, 12, and 14 weeks of 1-BP exposure (P < 0.05, P < 0.01), with the hindlimbs paralyzed after 16 weeks of 1-BP exposure. After 16 weeks of 1-BP exposure, the hindlimb grip strengths of rats in the medium-dose and low-dose groups were decreased to 72.6% and 91.2% of the control value (P < 0.01, P < 0.05). Compared with the control group, the high-dose group showed significantly increased hindlimb landing foot splay after 12, 14, and 16 weeks of 1-BP exposure, and the medium-dose group showed significantly increased hindlimb landing foot splay after 14 and 16 weeks of 1-BP exposure (P < 0.05, P < 0.01). The high-dose and medium-dose groups showed significantly higher serum alanine aminotransferase (ALT) activity than the control group after 8 weeks of 1-BP exposure, and so did the low-dose group after 16 weeks of 1-BP exposure (P < 0.01).

CONCLUSIONThe nervous system is sensitive to the toxic effect of 1-BP, and 1-BP exposure can induce peripheral neuropathy in rats.

Animals ; Disease Models, Animal ; Hydrocarbons, Brominated ; administration & dosage ; toxicity ; Male ; Peripheral Nervous System Diseases ; chemically induced ; physiopathology ; Rats ; Rats, Wistar