Malignant Transformation and Abnormal Expression of Eukaryotic Initiation Factor in Bronchial Epithelial Cells Induced by Cadmium Chloride

Objective To analyze the relationship between malignant transformation and abnormal expression of eukaryotic initiation factor 3 （eIF3 p36） in human bronchial epithelial （16HBE） cells induced by cadmium chloride （CdCl2）. Methods 16HBE cells were treated several times with different concentrations of CdCl2. Tumorigenic potential of transformed cells was identified by assays for anchorage-independent growth in soft agar and for tumorigenicity in nude mice after the 35th passage. Total RNA was isolated from 16HBE cells induced by CdC12, including non-transformed, Cd-transformed, and Cd-tumorigenic cell lines. Special primers for eIF3 p36 were designed and the expression of eIF3 mRNA in different cell lines was detected with fluorescent quantitative-polymerase chain reaction technique （FQ-PCR）. Results The 35th passage of 16HBE cells transformed by CdCl2 exhibited overlapping growth. Compared with the non-transformed cells, colonies of transformed cell lines in soft agar showed statistically significant increases and dose-dependent effects （P〈0.01）. All Cd-induced transformed cell lines formed rumors in nude mice within 2 weeks of inoculation, but none of the mice injected with non-transformed cells showed tumors even after 3 weeks. All tumors were pathologically identified as poorly differentiated squamous cell carcinoma. The eIF3 p36 genes in different stages of 16HBE cells transformed by CdCl2 were elevated as compared with the non-transformed control （P〈0.01）, and the eIF3 expression increased with the degree of cell malignancy. Conclusion CdCl2 is capable of inducing morphological transformation in 16HBE cells and transformed cells are potentially tumorigenic. Over-expression of eIF3 p36 is positively correlated with malignant transformation of 16HBE cells induced by CdCl2 and may be one of the molecular mechanisms potentially responsible for carcinogenesis due to Cd.

Alterative Expression and Sequence of Human Elongation Factor-1δ during Malignant Transformation of Human Bronchial Epithelial Cells Induced by Cadmium Chloride

Objective To study the alternative expression and sequence of human elongation factor-1δ （human EF-1δ p31） during malignant transformation of human bronchial epithelial cells induced by cadmium chloride （CdCl2） and its possible mechanism. Methods Total RNA was isolated at different stages of transformed human bronchial epithelial cells （16HBE） induced by CdCl2 at a concentration of 5.0 μM. Special primers and probe for human EF-1δ p31 were designed and expression of human EF-18 mRNA from different cell lines was detected with fluorescent quantitative PCR technique. EF-18 cDNA from different cell lines was purified and cloned into pMD 18-T vector followed by confirming and sequencing analysis. Results The expressions of human EF-1δ p31 at different stages of 16HBE cells transformed by CdCl2 was elevated （P〈0.01 or P〈0.05）. Compared with their corresponding non-transformed ceils, the overexpression level of EF-15 p31 was averagely increased 2.9 folds in Cd-pretransformed cells, 4.3 folds in Cd-transformed ceils and 7.2 folds in Cd-tumorigenic cells. No change was found in the sequence of overexpressed EF-1δ p31 at different stages of 16HBE cells transformed by CdCl2. Conclusion Overexpression of human EF-1δ p31 is positively correlated with malignant transformation of 16HBE cells induced by CdCl2, but is not correlated with DNA mutations.

The reproductive toxicity of cadmium chloride in male mice

Objective: To study the reproductive toxicity of cadmium chloride in male mice. Methods: Male mice of 4 weeks old were administered cadium chloride at doses of 0.5, 2 or 8 mg·kg-1·day-1 i.p. for 10 days. At day 50, the males were mated with virgin females at 1: 2. The pregnancy rate, the litter size and the body weight of the offspring were recorded; at the same time the development of the testis, the testicular index, the germ cell miosis and the epididymal sperm count, motility and malformed sperm were observed in the intoxicated males. Results: The testicular index was lower in the 2 and 8 mg/kg groups than in the controls and 0.5 mg/kg groups (P< 0.05). In the 2 and 8 mg/kg groups, there were testicular maldeve-lopment, epididymal azoospermia and infertility. The pregnancy rate was lower in the 2 mg/kg group than in the control and 0.5 mg/ kg group (P<0.05). The ectopic pregnancy rate of the cadmium chloride group was not significantly different from that of the controls. The sperm count, motility and malformed sperm were not significantly different between the 0.5 mg/kg group and the controls. Conclusion: Cadmium chloride, at doses of 2 mg/kg or more, reduces the pregnancy rate, which may be related to testis maldevelopment and epididymal azoospermia. Androl

Effect of Mercuric Chloride and Cadmium Chloride on Gonadal Function and Its Regulation in SexuallyMature Common Carp Cyprinus carpio

Gonadal function in fish, CJprinus carpio was significantly affected by sublethal doses of mercuric chloride (HgCl2 ) and cadmium chloride (CdCl2 ) in chronic (45 days ) exposure.Parameters investigated were nonesterified (NE) and esterified (E) cholestcrol of ovary,liver and serum and ovarian 3β-Hydroxysteroid and 17β-Hydroxysteroid dehyrogenaseenzyme activity and serum and pituitary gonadotropin (GtH) levels. Both the pollutantswere able to reduce the hypothalamic extract (HE) or gonadotropin releasing hormone(GnRH) induced pituitary GtH release in vitro. Short term (96h) exposure of the fish tothe pollutants had no significant effect on the gonadal function. ln addition to thedeleterious effect of pollutants on the gonadal steroidogenesis and pituitary gonadotropin release, using [4-14C] cholesterol as a tracer it was found that for 45 days expeure, HgCl2'had an adverse effect on the transport of cholesterol from circulation to ovary.

Cellular Oxidative Damage of HEK293T Cells Induced by Combination of CdCl_2 and Nano-TiO_2

This study investigated the conjoined cellular oxidative damage of human embryo kidney 293T（HEK293T） cells induced by cadmium chloride（CdCl2） and nanometer titanium dioxide（nano-TiO2）.RT-PCR technique was used to detect the expressions of Heme oxygenase-1（HO-1） and 8-oxoguanine DNA glycosylase（OGG1）.The activities of superoxide dismutase（SOD） and catalase enzyme（CAT） and concentrations of reactive oxygen species（ROS） and maldondialdehyde（MDA） were measured by different approaches.The results showed that CdCl2 and nano-TiO2 at a low concen-tration of 0.75 total toxic unit（TU） exerted an additive effects on HO-1 gene expression,CAT activities and MDA concentrations.When the total TU was increased to 1 or 1.25 TU,the interaction was syner-getic.Moreover,the mixture with high proportion of CdCl2 produced an additive effect on the OGG1 gene expression,and the interaction was changed to be synergetic when the concentration of CdCl2 was lower than or equal to that of nano-TiO2.Synergetic effects of CdCl2 and nano-TiO2 on cellular oxida-tive damage of HEK293T cells were found as indicated by the changes in the SOD activities and ROS concentrations.It was concluded that CdCl2 and nano-TiO2 exerts synergistic effects on the cellular oxidative damage of HEK293T cells,and the sensitivity of these indicators of oxidative damage varies with the proportion of CdCl2 and nano-TiO2 in the mixture.

Combined Effects of Cd and Hg on Liver and Kidney Histology and Function in Wistar Rats

The present study was performed in order to discern the effects of combined exposure to cadmium and mercury on liver function and histopathological alterations in male adult Wistar rats. In the present investigation, cadmium (100 mg/l) and mercury (25 mg/l) were administered orally for 10 weeks separately or in combination. The rational for studying cadmium and mercury is that both of these metals are encountered frequently in the same contaminated areas. In liver, the activities of serum alanine aminotransferase (ALT) and aspartate amino tranferase (AST) increased significantly in the cadmium (Cd) and mercury (Hg) alone or in combination (Cd + Hg) compared to the control suggesting that both cadmium and mercury cause hepatotoxicity spatially when co-administrated. We noted an increase in serum lactate dehydrogenase (LDH) activity in Cd and combined Cd + Hg treated groups while it decreased in Hg treated group. There was no statistically significant change in the level of total bilirubilin. Serum urea concentration showed a significant increase in the Cd and Hg groups compared to the control group. However an increase in serum creatinine concentration was noted only in the combined treated rats showing that renal insufficiency is more serious in the co-exposed group. Light microscopic examination indicated severe histological changes in the two organs under Cd and mercury influence. Results of the present investigation clearly showed that mercury has profound effects of hepatic handling of cadmium (synergistic effect) as shown by histological and biochemical results. Moreover, we observed a antagonist effect between these two toxic metals on kidney markers such as urea.

Effects of Cd^(2+) on the nucleolus in root tip cells of Allium cepa

The effects of different concentrations of cadmium chloride ranging from 0.5 to 20 ppm on the nucleolus in root tip cells of Allium cepa were studied using the silver staining technique. The results indicated that after the treatment with Cd￣(2+),different changes in nucleolar morphology appeared. The nucleolar material was extruded from the nucleus into the cytoplasm,and the nucleoli at mitotic metaphase did not disappear. Apparently,cadmium showed a specific effects on the nucleoli in root tip cells of Allium cepa. The possible mechanism behind this phenomenon is also briefly discussed.

Preventive effects of β-cryptoxanthin against cadmium-induced oxidative stress in the rat testis

β-cryptoxanthin （CRY）, a major carotenoid of potential interest for health, is obtained naturally from orange vegetables and fruits. A few research studies have reported that CRY could decrease oxidative stress and germ cell apoptosis. The purpose of this study was to examine the effects of CRY on acute cadmium chloride （CdCl2）-induced oxidative damage in rat testes. For this study, 24 rats were divided into four groups, one of which serves as a control group that received intraperitoneal （i.p.） injections of corn oil and physiological saline. The other rats were i.p. injected with CRY （10 μg kg^-1） every 8 h, beginning 8 h before CdCI2 （2.0 mg kg^-1） treatment. The pathological and TUNEL findings revealed that CRY ameliorated the Cd-induced testicular histological changes and germ cell apoptosis in the rats, Furthermore, the Cd-induced decrease in the testicular testosterone （T） level was attenuated after CRY administration （P 〈 0.05）. The administration of CRY significantly reversed the Cd-induced increases in the lipid peroxide （LPO） and malondialdehyde （MDA） levels （P 〈 0.01）. The testicular antioxidants superoxide dismutase （SOD）, catalase （CAT） and glutathione （GSH） were decreased by treatment with Cd alone but were restored by CRY co-treatment. These results demonstrated that the application of CRY can enhance the tolerance of rats to Cd-induced oxidative damage and suggest that it has promised as a pharmacological agent to protect against Cd-induced testicular toxicity.