Nephrotoxic effect of heavy metals and the role of DNA repair gene among secondary aluminum smelter workers.

This study aims to estimate the association between some heavy metals in suspended particulate matter (SPM) and kidney damage among workers at different departments in a secondary aluminum production plant. It also investigates the association between Xeroderma Pigmentosum complementation group D (XPD) gene polymorphisms and worker's susceptibility to kidney dysfunction. It was conducted on 30 workers from the administrative departments and 147 workers from different departments in the production line. Estimation of some heavy metals (Al, Co, Ni, Cu, Pb, and Cd) in suspended particulate matter (SPM) is done. Also, urinary levels of those metals were measured for all workers. Kidney injury molecule 1 (KIM-1), clusterin levels, and XPD protein level were estimated. Genotyping of XPD gene polymorphisms was performed. The measured annual average concentrations of the estimated heavy metals were lower than the permissible limits. Gravity area had the maximum concentration of metals with a higher Al average daily dose and hazardous index > 1. Kidney injury biomarkers (clusterin and KIM-1) were increased significantly (p < 0.05) while XPD protein showed the lowest levels among workers at the gravity and cold rolling areas. XPD Asn/Asp genotype was more dominant among those workers (85.7%). Conclusion: aluminum workers are at risk of kidney disorders due to heavy metal exposure. The individual's susceptibility to the diseases is related to the DNA repair efficiency mechanisms. The defect in XPD protein represents a good indicator of susceptibility to the disease. KIM-1 and clusterin estimation is a predictor biomarker for early-staged kidney diseases.

Lung cancer risk in workers occupationally exposed to polycyclic aromatic hydrocarbons with emphasis on the role of DNA repair gene.

OBJECTIVE: Workers in secondary aluminum production plants are occupationally exposed to polycyclic aromatic hydrocarbons (PAHs). We aimed to monitor the concentrations of PAHs in air and in serum of workers at two secondary aluminum production plants. We also investigated the potential risk of lung cancer development among PAHs exposed workers with emphasis on the role of A1AT mutation and APEX1 gene polymorphisms. METHODS: This study included 177 workers from administrative departments and production lines. Blood samples were obtained for estimation of benzo(a)pyrene diol epoxide albumin adduct (BPDE-Alb adduct), anti-Cyclin-B1 marker (CCNB1) and squamous cell carcinoma antigen (SCCAg). Genes' polymorphism for human apurinic/apyrimidinic endonuclease (APEX1) and alpha-1-anti-trypsin (A1AT) gene mutation were detected. RESULTS: There was a significant increase in the level of BPDE-Alb adduct among exposed workers in comparison to non-exposed group. Moreover, 41.67% of exposed workers in El Tebbin had BPDE-Alb adduct level ≥ 15 ng/ml versus 29.6% of workers in Helwan factory. There was a significant increase in tumor markers (SCCAg and CCNB1) among workers whose BPDE-Alb adduct ≥ 15 ng/ml. There was a significant increase in the level of BPDE-Alb adducts in exposed workers carrying homozygous APEX1 genotype Glu/Glu. Furthermore, exposed workers with the Glu/Glu genotype had high tumor markers levels. There was a significant increase in levels of BPDE-Alb adducts in workers carrying A1AT mutant allele. Moreover, workers with mutant A1AT genotype had significantly high tumor markers (SCCAg and CCNB1) levels. CONCLUSION: Therefore, we conclude that aluminum workers may be at a potential risk of lung cancer development due to PAHs exposure. Although PAHs concentrations in air were within the permissible limits, yet evidence of DNA damage was present as expressed by high BPDE-albumin adduct level in exposed workers. Also, elevation of tumor markers (SCCAg and CCNB1) in exposed workers points to the importance of periodic biological monitoring of such workers to protect them from cancer risk.

Influence of GSTM1, T1 genes polymorphisms on oxidative stress and liver enzymes in rural and urban pesticides-exposed workers.

Several studies discussed the relationship between the toxicity of organophosphates (OPs) and carbamates pesticides and oxidative stress which affects human health. This study aimed to evaluate the effects of pesticides on the induction of oxidative stress and hepatotoxicity. It was also focused on glutathione-S-transferase gene polymorphism in the modulation of these effects. In addition, the role of the educational level of exposed workers was studied. Acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), liver enzymes, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and glutathione S transferase (GST) were estimated at 100 pesticide-exposed workers (50 urban researchers (UE) and 50 rural sprayers (RE)), and 100 matched controls (50 urban controls (UC)and 50 rural controls (RC)). AChE and BuChE were decreased in RE and UE compared to RC. Aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activity were elevated in UE and UC compared to the RE and RC. Alanine aminotransferase (ALT) was elevated in UE compared to RE. MDA in RE and UE showed elevation compared to RC. There was a significant reduction in the levels of GSH, GST, and GPx in UE compared to RE and RC. The most sensitive pesticide-induced hepatotoxicity group were exposed workers with the GSTT1 genotype. Within these workers, ALT and ALP were significantly correlated with MDA and inversely correlated with AChE and BuChE, while AST was inversely correlated with AChE and BuChE only in UE. Conclusion: GST gene polymorphisms appeared to have a significant role in workers' susceptibility to hepatotoxic effects due to occupational exposure to pesticides; GSTT1 was the most sensitive genotype.

Alteration in antioxidant status in slow and fast alleles of EPHX1 gene polymorphisms among wood workers.

Occupational wood dust exposure may be associated with various health effects, especially in wood industry. These effects may be due to inducing oxidative stress which is related to inflammations. Biochemical assessment of antioxidant enzyme activities illustrated role of oxidative stress (OS) on its depletion. Super oxide dismutase, glutathione peroxidase (GPx) and catalase (CAT) were analyzed in 50 exposed workers and 50 control subjects. Also, macrophage inflammatory protein-2 was assessed among these workers as it was produced upon dust exposure. Microsomal epoxide hydrolase (EPHX1) enzyme shared in the protective mechanism against wood dust oxidative stress. It plays a dual role in the metabolism of environmental pollutants, detoxification, and bioactivation. Gene polymorphisms of EPHX1 may be associated with variations in enzyme activity. Polymorphisms in exons 3 and 4 have resulted in either decreased (slow conjugating allele) or increased (fast conjugating allele) activity in vitro. We aimed to evaluate the associations between EPHX1 polymorphisms and change in antioxidant status (SOD, CAT, and GPx) among wood dust exposed workers. EPHX1 genotyping in exon 3 and exon 4 polymorphisms was carried out by PCR-RFLP. Our result shows a significant reduction in enzymatic antioxidants (SOD, CAT, and GPx) levels with significant rise in MIP-2 levels in worker group. Also, there are significant variations in SOD, CAT, and GPx levels as well as in MIP-2 in different genotypes of EPHX polymorphisms in exon 3 or 4 (specially in Hist-Hist genotypes in both exons). We can conclude an alteration in antioxidant status in both slow and fast allele of EPHX gene polymorphisms with release of MIP-2 protein in wood workers.

Neurotoxicity of organic solvents with emphasis on the role of iron.

BACKGROUND: Exposure to organic solvents (OS) adversely affects different body systems, the central and peripheral nervous systems being the most susceptible ones. OBJECTIVES: This study investigated the role of iron in association with some neurotransmitters for diagnosis of neurotoxicity of OS. METHODS: The study included 90 workers, 50 occupationally exposed to OS and 40 representing control group. Blood samples were collected from the included subjects for determination of serum iron, total iron binding capacity (TIBC), serotonin and gamma-aminobutyric acid (GABA). RESULTS: Revealed reduction in serotonin level and serum iron. However, the elevation in GABA and TIBC was observed. The duration of exposure was significantly correlated with iron and serotonin while it was positively correlated with GABA and TIBC. CONCLUSIONS: Elevated GABA and TIBC with decreased serotonin and serum iron can be used as early diagnostic measures to detect the neurotoxic effects of OS.

Hepatotoxicity of aflatoxin B1 and its oxidative effects in wood dust Egyptian exposed workers.

The goal of the present study is to estimate the oxidative effects of AFB1 induced hepatotoxicity in furniture wood dust exposed workers. A cross-sectional comparative study was designed for comparing AFB1/albumin (AFB1/alb) levels and liver functions [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP)], malondialdehyde (MDA), glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in 88 furniture workers and 78 controls not occupationally exposed to wood dust. The AFB1/Alb, AST, ALT, MDA, and GPx were significantly higher; while, CAT significantly reduced in workers compared with controls. There was a significant correlation between AFB1/Alb and MDA level with the liver enzymes among both groups. CAT was inversely correlated with AFB1/Alb and the liver enzymes, and GPx was inversely correlated with AST in the workers. It was concluded that wood dust exposure is associated with raised serum levels of AFB1 and oxidative stress.

Evaluation of the effect of serum cystatin-C and ACE I/D and ACE G2350A polymorphisms on kidney function among hypertensive sewage workers.

Cadmium (Cd) as nephrotoxicant metal exerts its potent effect mainly on renal tubules disturbing its functions. A cross-sectional study was conducted on 55 sewage workers occupationally exposed to Cd and 50 control subjects. The study aimed to assess the effect of low-level Cd exposure on blood pressure and renal function in terms of serum cystatin-C levels. The associations between genetic polymorphisms of ACEI/D and ACE G2350A and hypertension and tubular injury among workers were studied. We analyzed blood and urine Cd concentration (U-Cd), serum cystatin-C, ACE I/D polymorphisms, and ACE G2350A, and blood pressure was measured. Results recorded a significant rise in serum and U-Cd and cystatin-C levels in sewage workers compared with controls. Significant distribution in genotype frequency of ACE I/D and ACE G2350A gene was detected. An association in DD genotype of ACE I/D with a rise in serum and U-Cd was observed in workers. In wild type genotype GG of ACE G2350A gene, a significant rise in serum cystatin-C levels and diastolic pressure was found while in heterozygote genotype GA significant rise in U-Cd levels was detected. Also, the association of AA genotype of ACE G2350A gene with a significant rise in serum and U-Cd and cystatin-C levels was shown among workers compared with control groups. Our findings indicated an association of ACE DD polymorphism in conjugation with GG genotype of ACE2 with hypertension and tubular injury in sewage workers.

Assessment of YKL-40, lipid profile, antioxidant status, and some trace elements in benign and malignant breast proliferation.

Breast cancer is mainly the common form of cancer in women and is a leading cause of death worldwide associated with cancer. The objective of this study was to assess the possible association of lipid profiles (total cholesterol TC, low-density lipoprotein LDL, very-low-density lipoprotein VLDL, high-density lipoprotein HDL, non-HDL and triglyceride TG), Chitinase-3-Like Protein1 (YKL-40) and changes in the levels of certain trace elements (Cu, Mg, Fe, and Zn), antioxidant status (TAC) and nitric oxide (NO) in benign and breast cancer in Egyptian females population. For 56 females with a benign breast tumor, 58 females with breast cancer, besides 52 healthy controls, Serum lipid profile, YKL-40, TAC, NO, Cu, Fe, Zn, and Mg have been determined. Our results showed a significant difference in lipid profile and a significant increase in, YKL-40, NO, and iron in breast benign tumor and cancer patients compared to control one. Besides, there is a significant reduction in serum magnesium and TAC levels in the patients' group compared to the healthy group. There is also a significant correlation between serum YKL-40 level and TC, LDL-C, VLDL-C, non-HDL-C, and TG in the breast cancer group; although only YKL-40 and VLDL-C showed a significant positive correlation in benign tumor patients. It is recommended that non-HDL-cholesterol, TAC, and Mg be used as biomarkers for breast cancer and its progression.

Early prediction of liver carcinogenicity due to occupational exposure to pesticides.

Several studies linked between pesticides exposure and development of liver cancer, through several mechanisms inform of genotoxicity, cytotoxicity, tumor promotion, immunotoxicity and hormonal actions. This study aimed to estimate novel biomarkers for early prediction of liver malignancy due to occupational exposure to pesticides in two groups of workers with different socioeconomic standard (highly educated urban researchers and low educated rural pesticides sprayers). This study included 50 urban researchers and 50 rural pesticides sprayers occupationally exposed to pesticides. They were compared with 50 non-exposed urban researchers and 50 non-exposed rural subjects. Several tumor biomarkers were estimated; P53 protein, Alfa fetoprotein (AFP), and Alpha-L-fucosidase (AFU). Additionally, telomerase enzyme activity, Relative telomere length (RTL), and DNA damage using comet assay were measured. Furthermore, the glutathione-S-Transferase (GST) gene polymorphisms were identified for both exposed groups. Statistical analysis revealed elevated level of tumor biomarkers among exposed subjects relative to control groups in spite of being within the normal range. Increase in the DNA damage was detected, with shortening of telomere length and decrease in telomerase enzyme activity in pesticides-exposed subjects compared to their controls. Most of these changes were related to the levels of butyrylcholinesterase. Subjects with GSTT1 genotype were suggested to be more susceptible to hepatic carcinogenicity. Telomere relative length and comets assay together with GST genes polymorphisms could be used as early predictors for liver cancer susceptibility among pesticides exposed workers.

Impact of occupational cadmium exposure on bone in sewage workers.

Cadmium (Cd) is one of the environmental risk factors for bone loss. The present study included 40 sewage workers occupationally exposed to Cd. Forty nonexposed men were included as a control group. Current smokers represented 65% and 47.5% of the exposed and control groups, respectively. The study aimed to investigate the hazard of occupational Cd exposure on bone health. This was achieved through measuring serum and urinary Cd, and calcium (Ca), in addition to serum osteoprotegerin (OPG) and estrogen receptor-α gene. Results showed significant elevation in serum Cd, OPG, and urinary Ca levels in the exposed compared to the controls. Bony aches and joint pain were more prevalent among the exposed workers. Serum and urinary Cd increased in exposed smokers relative to control smokers. Also, serum OPG levels showed significant rise among exposed smoker and nonsmoker compared to control smoker and nonsmoker groups. Serum Cd level increased significantly in PP and pp genotypes in exposed workers compared to controls, while elevated levels of serum OPG was observed in PP and Pp genotypes in exposed workers relative to controls. Urinary Cd exhibited significant rise in both PP and pp genotypes in exposed workers, while Ca excretion was elevated in pp genotype only. The study reflected an association of genetic predisposition and Cd exposure in progression of osteoporosis. Further research is needed to explain the mechanisms of Cd impact on bone. The role of smoking is important and hence smoking cessation programs are essential for sewage workers.

Effect of Occupational Cadmium Exposure on Parathyroid Gland.

BACKGROUND: Cadmium (Cd) is used in many industries. High-level exposure is associated with severe kidney and bone damage. AIM: This study investigates the possible effect of occupational cadmium exposure on parathyroid gland and some minerals in workers. METHODS: Environmental air monitoring of cadmium was done. Serum and urine cadmium levels, kidney function, some minerals, and plasma parathormone were estimated in the studied groups. RESULTS: The exposed workers had significantly higher Cd concentration in serum and urine than controls. The mean levels of plasma parathyroid hormone, serum phosphorus and magnesium were significantly lower among the exposed group. However, the mean levels of serum creatinine and calcium were significantly higher in the same group when compared to referents. There was a significant positive correlation between Cd concentration in the serum and urine for the exposed group. The biological Cd exposure indices correlated positively with serum calcium and negatively with plasma PTH level. The prevalence of musculoskeletal complaints, bone ache, joint pain and muscle spasm were more prevalent among the exposed workers compared with the controls with odds ratio 4.316, 3.053 and 3.103 respectively. CONCLUSIONS: Occupational cadmium exposure has an adverse effect on PTH level and serum human minerals.

Hormonal Perturbations in Occupationally Exposed Nickel Workers.

BACKGROUND: Nickel exposure is recognized as an endocrine disruptor because of its adverse effects on reproduction. AIM: This study was designed to investigate the possible testiculo-hormonal perturbations on workers occupationally exposed to nickel and to assess its effects on human male sexual function. METHODS: Cross-sectional comparative study, comprising 105 electroplating male non-smoker, non-alcoholic workers exposed to soluble nickel and 60 controls was done. Serum luteinizing hormone, follicle stimulating hormone, testosterone levels and urinary nickel concentrations were determined for the studied groups. RESULTS: Serum luteinizing hormone, follicle stimulating hormone, urinary nickel and the simultaneous incidence of more than one sexual disorder were significantly higher in the exposed workers compared to controls. The occurrence of various types of sexual disorders (decreased libido, impotence and premature ejaculation) in the exposed workers was 9.5, 5.1 and 4.4 folds respectively than the controls. CONCLUSIONS: Exposure to nickel produces possible testiculo-hormonal perturbations in those exposed workers.

Comparative Hepatotoxicity of Aflatoxin B1 among Workers Exposed to Different Organic Dust with Emphasis on Polymorphism Role of Glutathione S-Transferase Gene.

AIM: The study aimed to investigate effects of organic dust exposure from different sources on aflatoxin B1-albumin adducts (AFB1/Alb), and role of glutathione S-transferase (GST) gene polymorphism in hepatotoxicity of (AFB1) among exposed workers. MATERIAL AND METHODS: Liver enzymes, AFB1/Alb, and GST polymorphism were estimated in 132 wheat flour dust and 87 woods sawmill workers, and 156 controls. RESULTS: Results revealed that AFB1/Alb and liver enzymes were significantly elevated in exposed workers compared to controls, and were significantly higher in sawmill workers compared to flour workers. AFB1/Alb in flour and sawmill workers with GSTT1 and GSTM1&GSTT1 null genotypes were significantly higher than controls, and in sawmill workers with GSTM1&GSTT1 null than flour workers. Liver enzymes (ALT and AST) in sawmill workers were significantly higher than flour workers and controls in all GST polymorphism; except in GSTT1 polymorphism, where these enzymes were significantly higher in the two exposed groups than controls. CONCLUSIONS: In conclusion, organic dust exposure may cause elevation in AFB1/Alb and liver enzymes of exposed workers, and GST gene polymorphism plays an important role in susceptibility to hepatic parenchymal cell injury; except in workers with GSTT1&GSTM1 null genotype, gene susceptibility seemed to have little role and the main role was for environmental exposures.

Carcinogenic effects of aflatoxin B1 among wheat handlers.

BACKGROUND: Epidemiological studies have demonstrated that serum aflatoxin B1 (AFB1) is a hepatocarcinogenic mycotoxin and contributor to the high rate of hepatocellular carcinoma (HCC). The prevalence of liver cancer in Egypt is particularly worrisome. In a registry-based analysis of occupational risk for HCC, significant excesses were observed especially for grain mill workers. OBJECTIVE: The aim of this study was to assess the hepatic carcinogenicity of AFB1 in wheat handlers. METHODS: Serum AFB1/albumin (AFB1/Alb), alpha-fetoprotein (AFP), alpha-l-fucosidase (AFU), and arginase were estimated in exposed wheat handlers including millers and bakers. The control group was composed of non-occupationally exposed workers. RESULTS: AFB1/Alb and AFU were significantly higher among workers employed as bakers compared to mill workers and controls. Mill workers had higher levels of AFB1/Alb than the controls. AFB1/Alb, AFP, and AFU were all significantly higher and arginase was significantly lower among HCC cases compared to the other groups. There was a significant correlation between AFU and AFB1/Alb in bakers and between AFP and AFB1/Alb in HCC cases. Arginase was inversely correlated with AFB1/Alb in HCC cases. AFB1/Alb was significantly correlated with the duration of exposure in bakers. CONCLUSION: Wheat handlers exposed to Aspergillus flavus have a high risk of elevated serum AFB1/Alb levels and AFU.