Insulin expression in rats exposed to cadmium / 生物医学与环境科学（英文）

<p><b>OBJECTIVES</b>To investigate the effects of cadmium exposure on insulin expression in rats.</p><p><b>METHODS</b>Eighteen adult SD rats were administered cadmium subcutaneously (0.5, 1.0, and 2.0 mg/kg x bw). The effects on endocrine of pancreas were assessed. The levels of cadmium and zinc in pancreas, blood and urine glucose, serum insulin and urine NAG (N-acyetyl-beta-glucosaminidase) were determined. The gene expressions of metallothionein (MT) and insulin were also measured, and the oral glucose tolerance tests (OGTT) were carried out.</p><p><b>RESULTS</b>The contents of cadmium in pancreas in cadmium-treated rats were higher than that in the control group, which was associated with slight increase of zinc in pancreas. Cadmium-exposed rats (1.0 and 2.0 mg/kg x bw) demonstrated a marked glucose intolerance. But the levels of serum insulin did not change significantly after cadmium administration, and the UNAG had no change in Cd-treated group. The gene expression of insulin decreased in 1.0 and 2.0 mg/kg x bw cadmium-exposed groups, compared with the control group. The expression of MT-I was higher in the groups exposed to 1.0 and 2.0 mg/kg x bw cadmium while the expression of MT-II was higher in the group exposed to 2.0 mg/kg x bw cadmium.</p><p><b>CONCLUSIONS</b>Cadmium may be accumulated in the pancreas, resulting in the change of the expression of insulin, MT-I and MT-II genes. Cadmium can influence the biosynthesis of insulin, but does not induce the release of insulin. The dysfunction of pancreas occurs earlier than that of kidney after administration of cadmium.</p>

Inhibitory effect of isoflavones on prostate cancer cells and PTEN gene / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To explore the mechanisms by which genistein and daidzein inhibit the growth of prostate cancer cells.</p><p><b>METHODS</b>LNCaP and PC-3 cells were exposed to genistein and daidzein and cell viability was determined by MTT assay and cytotoxicity of the drugs by LDH test. Flow cytometry (FCM) was used to assess the cell cycle in LNCaP and PC-3 cells. Reverse transcription-polymerase chain reaction (RT-PCR) was applied to examine the expression of PTEN gene (a tumor suppressor gene), estrogen receptor alpha gene (ERalpha), estrogen receptor beta gene (ERbeta), androgen receptor gene (AR) and vascular endothelial growth factor gene (VEGF).</p><p><b>RESULTS</b>The viability of PC-3 and LNCaP cells decreased with increasing concentrations and exposure time of genistein and daidzein. Genistein increased G2/M phase cells in PC-3 cells while decreased S phase cells in LNCaP cells in a dose-dependent manner. Daidzein exerted no influence on the cell cycle of LNCaP and PC-3 cells, but the apoptosis percentage of LNCaP cells was elevated significantly by daidzein. Genistein induced the expression of PTEN gene in PC-3 and LNCaP cells. Daidzein induced the expression of PTEN gene in LNCaP but not in PC-3 cells. The expression of VEGF, ERalpha and ERbeta genes decreased and AR gene was not expressed after incubation with genistein and daidzein in PC-3 cells. In LNCaP cells, the expression of VEGF and AR gene decreased but there was no change in the expression of ERalpha and ERbeta gene after incubation with genistein and daidzein. Conclusion Genistein and daidzein exert a time- and dose-dependent inhibitory effect on PC-3 and LNCaP cells. The down-regulation of ER gene by daidzein influences the growth of PC-3 cells directly. The inhibition of PC-3 cells by genistein and that of LNCaP cells by genistein and daidzein may be via Akt pathway that is repressed by PTEN gene, which subsequently down-regulates the expression of AR and VEGF genes. Our results suggest that the expression of PTEN gene plays a key role and several pathways may be involved in the suppression of prostate cancer cells by genistein and daidzein.</p>

Metallothionein 1 isoform gene expression induced by cadmium in human peripheral blood lymphocytes / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the gene expression of metallothionein 1 (MT-1) isoforms in human peripheral blood lymphocytes (HPBLs).</p><p><b>METHODS</b>The expression of mRNA representing the seven active MT-1 genes was determined in HPBLs by quantitative RT-PCR before and after exposure to cadmium.</p><p><b>RESULTS</b>Basal expressions of MT-1X, and MT-1A in HPBLs were similar to expression of housekeeping gene. In contrast, the basal gene expressions of MT-1H, 1F, 1E, and 1G were a little transcripts in human HPBLs. No signal was detected for MT-1B. There was a sex difference (P < 0.05). in basal gene expression of MT-1E. The levels of gene expression of MT-1A, 1E, 1F, 1G, 1H, and 1X increased, but the level of MT-1B did not increase after exposure to cadmium.</p><p><b>CONCLUSIONS</b>Gene expressions of MT-1G, MT-1H, MT-1F, and MT-1X in HPBLs can be used as a potential biomarker of cadmium exposure.</p>

The effects of cadmium on the levels of insulin in smelters / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effects of cadmium on the levels of insulin and blood glucose in exposed workers.</p><p><b>METHODS</b>Ninety-eight cadmium-exposed workers in a smeltery in the mid-south district of our country were selected as the exposed subjects while the healthy doctors in the workers hospital who were not exposed to the cadmium were treated as the control. The subjects were grouped according to the exposure time, the blood cadmium and the urine cadmium. The variety of the level of serum insulin was investigated for the workers in different groups of the exposure time, the blood cadmium and the urine cadmium. The variety of the levels of the blood zinc and urine zinc were also determined. The relationships among the blood cadmium, the blood zinc and the serum insulin were analyzed.</p><p><b>RESULTS</b>The level of blood glucose in the group of the exposure time of more than 20 years [(4.9 +/- 0.6) mmol/L] was significantly higher than that in the control group [(4.6 +/- 0.60) mmol/L] with significantly statistical difference (P < 0.01). The level of serum insulin in the group of the exposure time of more than 10 years [(8.58 +/- 4.91) microIU/ml] was significantly lower than that in the control group [(11.57 +/- 5.42) microIU] with the significantly statistical difference (P < 0.05) and the level of serum insulin would be decreased significantly with the increase of the blood cadmium and urinary cadmium. The level of the urine zinc was increased significantly in the workers of the exposure time of more than 20 years. The correlation analysis indicated that the negative correlation was found between the level of serum insulin and the level of blood cadmium, as well as between the level of the serum insulin and the level of the urinary cadmium; the positive correlation was found between the level of blood glucose and the level of insulin, as well as between the level of blood glucose and the level of C peptide in serum.</p><p><b>CONCLUSION</b>The exposure to cadmium can cause the decrease of serum insulin and may affect the level of blood glucose.</p>

Relationship between plasma anti-metallothionein antibody and renal dysfunction in cadmium exposed workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate whether renal dysfunction induced by cadmium is related to plasma anti-metallothionein antibody (anti-MT Ab) in workers occupationally exposed to cadmium.</p><p><b>METHODS</b>The male workers in a smeltery were selected as the subjects for the exposure and effect assessment. The urine cadmium (UCd), the blood cadmium (BCd) and the occupational cadmium intake (TTCd) served as the exposure indexes while the urine beta(2) microglobulin (Ubeta(2)-MG), the N-acetyl-beta-D-glucosaminidase (UNAG) and the urine albumin concentration (UALB) served as the effect markers for the renal dysfunction caused by the cadmium. The titer of the plasma anti-metallothionein antibody was determined with the enzyme linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>The UCd (3.16 microg/g Cr), BCd (9.28 microg/L), Ubeta(2)-MG (81.17 microg/g Cr) and UALB (7.03 mg/g Cr) in the occupational cadmium exposure group were significantly higher than those in the control group and the Ubeta(2)-MG, UNAG and UALB as well as the occurrence rate of abnormality would be increased with the increase of the level of the occupational cadmium exposure. There was no significant difference in the titer of anti-MT Ab between the exposure group and the control group (P > 0.05). The titer of the anti-MT Ab would not be increased with the increase of the dosage of the exposure and had no significant correlation with BCd, UCd and TTCd (P > 0.05). The positive correlation were found between anti-MT Ab and UNAG as well as between anti-MT Ab and Ubeta(2)-MG in the exposure group with the correlation coefficient of 0.302 and 0.218 respectively. The workers with high level anti-MT Ab are more susceptible to cadmium nephrotoxicity than those with low anti-MT Ab with the odds ratio (OR) value of 4.200 and the 95% CI between 1.213 and 14.541 (P < 0.05).</p><p><b>CONCLUSION</b>There is a dose-effect relationship between cadmium exposure and renal dysfunction in workers occupationally exposed to cadmium, but no correlation is found between cadmium exposure and plasma anti-MT Ab. The workers occupationally exposed to the cadmium with higher level of anti-MT Ab are easier to suffer from renal dysfunction caused by cadmium. Plasma anti-MT Ab could be used as a biomarker of susceptibility in the workers exposed to cadmium.</p>

Application of metallothionein gene isoforms expression as biomarkers in cadmium exposure / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the feasibility of metallothionein (MT) gene expression level in human peripheral blood lymphocytes (HPBLs) as a biomarker in cadmium exposure.</p><p><b>METHODS</b>The MT gene expression level in HPBLs of workers exposed to cadmium was examined using RT-PCR technique, and the exposure assessment and effect assessment were conducted in exposed workers.</p><p><b>RESULTS</b>The basal MT-1A, IE, IF, IX and MT-2A expression level in workers exposed to cadmium were significantly higher than those in the control group (P < 0.05). The basal MT-1A, IE, IF, IX and MT-2A expression level would be significantly increased with the increase of the blood cadmium (BCd) level (P < 0.05). There was a trend of increase for the mRNA expression of the basal MT-1A, 1E, IF, IX, MT-2A, especially for the mRNA expression of MT-1A and MT-2A (P < 0.05) with the increase of the level of the urine cadmium (UCd). There was a good dose-response relationship between basal MT-1A expression and UCd. The basal MT-1A, IE, IF, IX and MT-2A expression level were significantly correlated with BCd (P < 0.05) while the basal MT-1A, IF and MT-2A expression level were significantly correlated with UCd (P < 0.05). There were dose-effect relationships of BCd to the basal MT-1E, MT-1F, MT-1X and MT-2X expression level respectively and there were also dose-effect relationships of UCd, beta(2)-MG and the urine metallothionein to the basal MT-1A expression.</p><p><b>CONCLUSION</b>The expression of the MT gene isoforms in HPBLs can serve as the biomarker for the cadmium exposure and MT-1A can also serve as the effective biomarkers for the cadmium-induced renal toxicity.</p>

Comparison on urinary 1-hydroxypyrene concentrations between coke oven workers and non-occupational exposed individuals / 中华预防医学杂志

<p><b>OBJECTIVE</b>To compare the urinary 1-hydroxypyrene (1-OHP) concentrations between coke oven workers and non-occupational exposed individuals and to investigate the possible impact factors.</p><p><b>METHODS</b>Spot end-of-shift urine samples were collected in 265 coke oven workers and spot morning urine samples in 226 non-occupational exposed individuals. External exposure levels and possible confounding factors were assessed by environmental polycyclic aromatic hydrocarbons (PAH) monitoring and uniform questionnaire, and the urinary 1-OHP concentrations determined by high performance liquid chromatography (HPLC), were used to compare the different urinary 1-OHP levels between different research populations and to explore the effects of several factors such as external exposure levels, smoking habits, alcohol consumptions, age and body mass index (BMI).</p><p><b>RESULTS</b>The urinary 1-OHP concentrations in coke oven workers were significantly higher than those in non-occupational exposed individuals (13.49, 6.56, 1.38 and 0.35 micromol/mol creatinine for topside workers, side-oven workers, bottom side workers and references, respectively, P < 0.001; the same trends for the percentage of the level over 2.3 micromol/mol creatinine: 94.81%, 84.73%, 35.09% and 0.88%, P < 0.001). The control individuals who smoked over 20 cigarettes per day possessed higher urinary 1-OHP concentrations than the non-smokers (adjusted geometric mean: 0.47 and 0.31 micromol/mol creatinine, respectively, P < 0.05). Alcohol drinking references possessed lower urinary 1-OHP levels than the non-drinkers (adjusted geometric mean: 0.33 and 0.47 micromol/mol creatinine, respectively, P < 0.05).</p><p><b>CONCLUSION</b>Coke oven workers should be exposed to a high level of urinary 1-OHP, especially for topside workers and side-oven workers. Background urinary 1-OHP levels in non-occupational exposed individuals should be related to smoking habits and alcohol consumptions.</p>

The toxic effects of cadmium on pancreas / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>In order to explore the toxic effects of cadmium on functions of endocrine and exocrine of pancreas.</p><p><b>METHODS</b>96 SD rats were administered with cadmium at different doses (0, 50, 100, 200 mg/L) by drinking water for 30 days, 60 days and 90 days. The contents of cadmium and zinc in the blood and pancreas, also the glucose level in blood and urine, the levels of insulin and the activity of amylase were determined. The gene expression of metallothionein (MT), insulin and pancreatic amylase were also measured.</p><p><b>RESULTS</b>The results showed that the contents of cadmium in the serum and pancreas were higher than that of the control groups (P < 0.05). The contents of zinc in serum were decreased in the groups of 100 and 200 mg/L cadmium at the 90-day. As well as increased zinc in pancreas. The gene expression of insulin was not different compared with those of the control group except the middle-dose group at the 60-day. And the expression of amylase were higher in the groups of 100 and 200 mg/L cadmium at the 60-day and the 90-day. The expression of MT-1 and -2 were higher in the pancreas after cadmium administration.</p><p><b>CONCLUSION</b>It is suggested that cadmium could be accumulated in the pancreas and caused the change of the zinc levels. Then it resulted in the change of the expression of gene and protein, and influence of the functions of both endocrine and exocrine in pancreas.</p>

Occupational exposure profiles of polycyclic aromatic hydrocarbons in coke oven workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the characteristics of occupational exposure of polycyclic aromatic hydrocarbons (PAHs) in coke oven workers.</p><p><b>METHODS</b>Samples were collected individually and PAHs concentration in the ambient air were assayed by high performance liquid chromatography (HPLC) and toxic equivalency factors (TEFs) were introduced to assess the carcinogenic potency.</p><p><b>RESULTS</b>The levels of PAHs occupational exposure in oven workers at topside was higher than at side oven and bottom oven (P < 0.05). Non-carcinogenic PAHs were more than 70% of total PAHs and benzo[a]pyrene accounted for 65.5% approximately 72.4% of total benzo[a]pyrene equivalents. Total occupational exposure level of PAHs in coke oven workers was positively related to the content of benzo[a]pyrene and pyrene, respectively (r(2) = 0.84, r(2) = 0.94, P < 0.05).</p><p><b>CONCLUSION</b>Coke oven workers were exposed to a high level of PAHs which possessed some extent of carcinogenic potency, and benzo[a]pyrene is the chief carcinogenic substance.</p>

Modulation of isoflavones on bone-nodule formation in rat calvaria osteoblasts in vitro / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To observe the effects of two main isoflavones, daidzein and genistein on the bone-nodule formation in rat calvaria osteoblasts in vitro.</p><p><b>METHODS</b>Osteoblasts obtained from newborn Sprague-dawley rat calvaria were cultured for several generations. The second generation cells were cultured in Minimum Essential Medium supplemented with ascorbic acid and Na-beta-glycerophosphate for several days, in the presence of daidzein and genistein, with or without the estrogen receptor antagonist ICI 182780. Number of nodules was counted at the end of the incubation period (day 20) by staining with Alizarin Red S calcium stain. The release of osteocalcin, as a marker of osteoblast activity, was also determined on day 7 and day 12 during the incubation period.</p><p><b>RESULTS</b>Compared with the control, the numbers of nodules were both increased by incubation with daidzein and genistein. 17 beta-estradiol was used as a positive control and proved to be a more effective inducer of the increase in bone-nodules formation that daidzein and genistein. The release of osteocalcin into culture media was also increased in the presence of daidzein and genistein, as well as 17 beta-estradiol on day 7 and day 12 (day 12 were higher). The estrogen receptor antagonist ICI 182780 completely blocked the genistein- and 17 beta-estradiol-induced increase of nodule numbers and osteocalcin release in osteoblasts. However, the effects induced by daidzein could not be inhibited by ICI 182780.</p><p><b>CONCLUSION</b>These findings suggest that geinistein can stimulate bone-nodule formation and increase the release of osteocalcin in rat osteoblasts. The effects, like those induced by 17 beta-estradiol, are mediated by the estrogen receptor dependent pathway. Daidzein also can stimulate bone-nodule formation and increase the release of osteocalcin in rat osteoblasts, but it is not, at least not merely, mediated by the estrogen receptor dependent pathway.</p>