Effect of simultaneous silencing of HPV-18 E6 and E7 on inducing apoptosis in HeLa cells.

The objective of this investigation was to determine if simultaneous silencing of the human papillomavirus type 18 (HPV-18) E6 and E7 oncogenes using RNA interference (RNAi) would be a potential therapeutic approach against the carcinogenic activity of this virus. Two synthetic double-stranded oligonucleotides, encoding short hairpin transcripts corresponding to HPV-18 E6 and E7 genes, were cloned into pGenesilence (pGS) 1.0 vectors to produce pGS-E6, pGS-E7, and pGS-(E6+E7), respectively. Our results showed that the expression of HPV-18 E6 class 1 and HPV-18 E7 in HeLa cells was markedly decreased after being transfected with pGS-E6, pGS-E7, and pGS-(E6+E7) vectors. Of the three vectors, pGS-(E6+E7) had a greater ability to decrease the growth rate of HeLa cells, inhibit colony formation in soft agar, and significantly reduce tumor growth in nude mice. We also found that depletion of HPV-18 E6 and E7 in this manner promoted apoptosis of HeLa cells. Our data showed that simultaneously decreasing HPV-18 E6 and E7 gene expression in HeLa cells by RNAi could significantly inhibit tumor growth under in vitro conditions and in nude mice. These data suggest that gene therapy may be a possible therapeutic approach for HPV-positive cervical cancers.

Lead and cadmium synergistically enhance the expression of divalent metal transporter 1 protein in central nervous system of developing rats.

Divalent metal transporter 1 (DMT1) can transport a large range of ions, including toxic lead (Pb) and cadmium (Cd), across membranes. In this study, a total of 24 rats were divided into four groups for intragastrical perfusion treatment: control, Pb alone, Cd alone, and Pb + Cd. Pb and Cd contents in blood were detected, and the mRNA and protein levels of DMT1 were analyzed in the cerebellum, cortex, and hippocampus. Both Pb and Cd levels were elevated in all groups perfused with Pb and/or Cd, except for Pb level in the Cd-alone group (P < 0.05). The mRNA level of DMT1 did not differ among the four groups (P > 0.05). However, the DMT1 protein expression was significantly increased by 0.9-, 1.0-, and 1.1-fold in cerebellum, cortex, and hippocampus of the Pb + Cd group than in controls, respectively. Pb and Cd exposure can synergistically induce DMT1 protein synthesis and has implications for transportation of toxic ions in the developing rat's brain.

The hazard of chromium exposure to neonates in Guiyu of China.

Guiyu is one of the most heavily chromium-polluted areas in China due to the presence of numerous electronic waste (e-waste) recycling sites in the region. In this study, we investigate the effect of umbilical cord blood chromium levels (UCBCLs) on neonates from Guiyu and discuss chromium-induced DNA damage of cord blood lymphocyte. Umbilical cord blood samples were collected from neonates of Guiyu (in 2006, n=100; in 2007, n=100) and the neighboring town of Chaonan (in 2006, n=52; in 2007, n=50) that is associated with the fishery. UCBCLs of the neonates were determined by graphite atomizer absorption spectrophotometer. Comet experiment was used to examine lymphocyte DNA damage. Questionnaires to gauge chromium exposure were administered to the mothers of the neonates. The mean UCBCLs of neonates in the Guiyu group in 2006 and 2007 were 303.38 microg/L and 99.90 microg/L with median 93.89 microg/L and 70.60 microg/L, respectively. We observed significant differences between the results in UCBCLs of neonates in Guiyu and the control group (P<0.01). There was no significant difference of UCBCLs in neonates between 2006 and 2007 in Guiyu (P>0.05). Higher levels of chromium in neonates were found to correlate with their mothers' exposure to e-waste recycling. There were significant differences in terms of DNA damage between the Guiyu group and the control group (P<0.05). There was a correlation between DNA damage and the UCBCLs of neonates (P<0.05). There is conclusive evidence that high UCBCLs in neonates exists in e-waste recycling areas in Guiyu and that e-waste recycling activity poses serious environmental problems. Chromium pollution is threatening the health of neonates around the recycling sites.

Blood lead and cadmium levels and relevant factors among children from an e-waste recycling town in China.

BACKGROUND: Primitive electronic waste (e-waste) recycling is ongoing in Guiyu, and thus toxic heavy metals may keep on threatening to the health of local children. Some related factors may contribute to the elevation of blood lead levels (BLLs) or blood cadmium levels (BCLs). OBJECTIVE: To investigate the children's BLLs and BCLs in Guiyu and Chendian as compare to discuss the effects of primitive e-waste recycling activities on children's health. METHODS: Two hundred and seventy-eight children less than 8 years who lived in Guiyu and Chendian were observed, and their BLLs and BCLs were determined by graphite atomizer absorption spectrophotometer. Questionnaire survey for risk factors was also performed and data were analyzed using spearman correlation analyses and logistic regression analyses. RESULTS: Children living in Guiyu had significantly higher BLLs and BCLs as compared with those living in Chendian (p<0.01). In Guiyu, 70.8% of children (109/154) had BLLs>10 microg/dL, and 20.1% of children (31/154) had BCLs>2 microg/L, compared with 38.7% of children (48/124) had BLLs>10 microg/dL and 7.3% of children (9/124) had BCLs>2 microg/L in Chendian (p<0.01, respectively). We also observed a significant increasing trend in BLLs with increasing age in Guiyu (p<0.01). Mean height of children in Guiyu was significantly lower than that in Chendian (p<0.01). The risk factors related to children's BLLs and BCLs mainly included father's engagement in the work related to e-waste, children's residence in Guiyu and the amount of time that children played outside near the road everyday. CONCLUSIONS: There are close relationships between the BLLs, BCLs in children and the primitive e-waste recycling activities in Guiyu. Environmental pollution, especially lead pollution, has threatened the health of children living around e-waste recycling site.

[Determination of meconium lead level of newborn by graphite furnace atomic absorption spectrometry].

UNLABELLED: To establish a method for the determination of lead in meconium from 144 samples of newborn through nitric acid digestion by means of graphite furnace atomic absorption spectrometry. METHODS: after being baked for at least 12 h at 60 degrees C, 0.3 g of meconium was digested by nitric acid and hydrogen peroxide in turn at 80 degrees C under water-bath condition for 1h and then metered to the whole volume of to 2 mL. After correcting the background with D2 lamp, specimen basal corpuscle matched standard curve was used to detect the lead content. RESULTS: The mean lead content of 93 experimental samples was 1.934 microg x g(-1) with the standard deviation (SD) of 1.551, and that of the 51 control samples was 1.012 microg x g(-1), with the SD of 1.084. There was a significant difference in lead levels of in meconnt between the experimental group and control group (p = 0.000). CONCLUSION: The lead content of the experimental was significantly higher than that of the control group detected by this method. This method was stable and efficient.

Monitoring of lead load and its effect on neonatal behavioral neurological assessment scores in Guiyu, an electronic waste recycling town in China.

Guiyu is the major electronic waste (e-waste) recycling town in China. The primary purpose of this study was to measure the lead levels in neonates and examine the correlation between lead levels and neurobehavioral development. One hundred full-term neonates from Guiyu and fifty-two neonates from neighboring towns (control group) in the late summer of 2006 were selected for study. The lead levels in the umbilical cord blood (CBPb) and lead levels in meconium (MPb) of neonates were determined with atomic absorption spectrophotometry. The neonatal behavioral neurological assessment (NBNA) was conducted on all neonates. A questionnaire related to the exposure to lead of pregnant women was used as a survey of the neonates' mothers. Compared with the control group, neonates in Guiyu had significantly higher levels of lead (P < 0.01), and the mean CBPb and MPb were 113.28 microg L(-1) and 2.50 microg g(-1), respectively. The relatively high lead levels in the neonates of the Guiyu group were found to correlate with their maternal occupation in relation to e-waste recycling. Neonates with high levels of lead load have lower NBNA scores (P < 0.01). There was a statistically significant difference in NBNA scores between the Guiyu group and the control group by t test (P < 0.05). No correlation was found between CBPb and NBNA scores; however, a negative correlation was found between MPb and NBNA scores (P < 0.01). There is a correlation between relatively high lead levels in the umbilical cord blood and meconium in neonates and the local e-waste recycling activities related to lead contamination. This study suggests that environmental lead contamination due to e-waste recycling have an impact on neurobehavioral development of neonates in Guiyu.