Comparison of T-2 Toxin and HT-2 Toxin Distributed in the Skeletal System with That in Other Tissues of Rats by Acute Toxicity Test.

Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system (thighbone, knee joints, and costal cartilage) were significantly higher than those in the heart, liver, and kidneys (P < 0.05). The relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system (thighbone and costal cartilage) were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%.

Comparison of Apoptosis and Autophagy in Human Chondrocytes Induced by the T-2 and HT-2 Toxins.

In this report, we have investigated the apoptosis and autophagy of chondrocytes induced by the T-2 and HT-2 toxins. The viability of chondrocytes was measured by the MTT assay. Malondialdehyde (MDA) and superoxide dismutase (SOD) kits were used to measure the oxidative stress of chondrocytes. The apoptosis of chondrocytes was measured using flow cytometry. Hoechst 33258 and MDC staining agents were introduced to analyze apoptosis and autophagy induction in chondrocytes, respectively. Protein expression of Bax, caspase-9, caspase-3, and Beclin1 was examined by western blotting analysis. The T-2 and HT-2 toxins significantly decreased the viability of chondrocytes in a time-dependent manner. The level of oxidative stress in chondrocytes induced by the T-2 toxin was significantly higher when compared with that of the HT-2 toxin. The apoptosis rate of chondrocytes induced by the T-2 toxin increased from 3.26 ± 1.03%, 18.38 ± 1.28%, 34.5 ± 1.40% to 49.67 ± 5.31%, whereas apoptosis rate of chondrocytes induced by the HT-2 toxin increased from 3.82 ± 1.03%, 11.61 ± 1.27%, 25.72 ± 2.95% to 36.28 ± 2.81% in 48 h incubation time. Hoechst 33258 staining confirmed that apoptosis of chondrocytes induced by the T-2 toxin was significantly higher than that observed when the chondrocytes were incubated with the HT-2 toxin. MDC staining revealed that the autophagy rate of chondrocytes induced by the T-2 toxin increased from 6.38% to 63.02%, whereas this rate induced by the HT-2 toxin changed from 6.08% to 53.33%. The expression levels of apoptosis and autophagy related proteins, Bax, caspase-9, caspase-3, and Beclin1 in chondrocytes induced by the T-2 toxin were significantly higher when compared with those levels induced by the HT-2 toxin.

Selenium promotes metabolic conversion of T-2 toxin to HT-2 toxin in cultured human chondrocytes.

To explore the metabolism of T-2 toxin in human chondrocytes (HCs) and determine the impact of selenium supplementation. For determination of cytotoxicity using the MTT assay, optical density values were read with an automatic enzyme-linked immunosorbent assay reader at 510nm. Cell survival was calculated and the cytotoxicity estimated. To identify the metabolites of T-2 toxin, the medium supernatants and C28/I2 cells were analyzed by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) separately. For HPLC-MS/MS, the mobile phase A was water and phase B was 98% methanol. The gradient for the elution was: 0-0.5min, 50% of B; 0.5-2.0min, 100% of B; 2.0-3.5min, 100% of B; 3.6-6min, 50% of B. T-2 toxin increased the toxicity to C28/I2 cells significantly in a dose- and time-dependent manner (viability range 91.5-22.0%). Supplementation with selenium (100ng/mL) could increase the cell viability after the 24h incubation. The concentration of T-2 toxin in the cell medium decreased from 20 to 6.67±1.02ng/mL, and the concentration of HT-2 toxin increased from 0 to 6.88±1.23ng/mL during the 48h incubation, whereas the relative concentration of T-2 toxin in cells increased from 0 to 12.80±1.84ng/g. Supplementary selenium in the HCs cultures reduced the cytotoxicity induced by T-2 toxin significantly, and was associated with rapid conversion of T-2 toxin in the culture medium to HT-2 toxin. T-2 toxin was more toxic to HCs than HT-2 toxin at equivalent concentrations. HT-2 toxin was a detectable metabolite of T-2 toxin in cultured HCs, and selenium enhanced the metabolic conversion of T-2 toxin, reducing its cytotoxicity to HCs.

Lack of any association of GST genetic polymorphisms with susceptibility to ovarian cancer--a meta-analysis.

OBJECTIVE: Epidemiology studies have reported conflicting results between glutathione S-transferase Mu-1 (GSTM1), glutathione S-transferase theta-1 (GSTT1) and glutathione S-transferase pi-1 (GSTP1) and ovarian cancer (OC) susceptibility. In this study, an updated meta-analysis was applied to determine whether the deletion of GSTM1, GSTT1 and GSTP1 has an influence on OC susceptibility. METHODS: A published literature search was performed through PubMed, Embase, Cochrane Library, and Science Citation Index Expanded database for articles published in English. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random or fixed effects models. Heterogeneity between studies was assessed using the Cochrane Q test and I2 statistics. Sub-group analysis was conducted to explore the sources of heterogeneity. Sensitivity analysis was employed to evaluate the respective influence of each study on the overall estimate. RESULTS: In total, 10 published studies were included in the final analysis. The combined analysis revealed that there was no significant association between GSTM1 null genotype and OC risk (OR=1.01, 95%CI: 0.91-1.12). Additionally, there was no significant association between GSTT1 genetic polymorphisms and OC risk (OR=0.98, 95% CI: 0.85-1.13). Similalry, no significant associations were found concerning the GSTP1 rs1695 locus and OC risk. Meanwhile, subgroup analysis did not show a significant increase in eligible studies with low heterogeneity. However, sensitivity analysis, publication bias and cumulative analysis demonstrated the reliability and stability of the current meta-analysis. CONCLUSIONS: These findings suggest that GSTs genetic polymorphisms may not contribute to OC susceptibility. Large epidemiological studies with the combination of GSTM1 null, GSTT1 null and GSTP1 Ile105Val polymorphisms and more specific histological subtypes of OC are needed to prove our findings.

Geographic distribution and epidemiology of lung cancer during 2011 in Zhejiang province of China.

BACKGROUND: To explore etiology for providing scientific clues for the prevention of lung cancer. MATERIALS AND METHODS: Data for lung cancer incidence and meteorological geographic factors from 25 counties in Zhejiang province of China during 2011 were studied. Stepwise multiple regression and correlation analysis were performed to analyze the geographic distribution and epidemiology of lung cancer. RESULTS: 8,291 new cases (5,998 in males and 2,293 females) of lung cancer during 2011 in Zhejiang province were reported in the 25 studied counties. Reported and standardized incidence rates for lung cancer were 58.0 and 47.0 per 100,000 population, respectively. The incidence of lung cancer increased with age. Geographic distribution analysis shows that the standardized incidence rates of lung cancer in northeastern Zhejiang province were higher than in the southwestern part, such as in Nanhu, Fuyang, Wuxing and Yuyao counties, where the rates were more than 50 per 100,000 population. In the southwestern Zhejiang province, for instance, in Yueqing, Xianju and Jiande counties, the standardized incidence rates of lung cancer were lower than 37 per 100,000 population. Spearman correlation tests showed that forest coverage rate, air quality index (AQI), and annual precipitation level are associated with the incidence of lung cancer. CONCLUSIONS: Lung cancer in Zhejiang province shows obvious regional differences. High incidence appears associated with low forest coverage rate, poor air quality and low annual precipitation. Therefore, increasing the forest coverage rate and controlling air pollution may play an important role in lung cancer prevention.