Exposure of Male Farmers and Nonfarmers to Neonicotinoid Pesticides in the South-West and Littoral Regions of Cameroon: A Comparative Study.

Pesticides, especially the newly developed neonicotinoids, are increasingly used in many countries around the world, including Cameroon, to control pests involved in crop destruction or disease transmission. Unfortunately, the pesticides also pose tremendous environmental problems because a predominant amount of their residues enter environmental matrices to affect other nontargeted species including humans. This therefore calls for continuous biomonitoring of these insecticides in human populations. The present study sought to assess the neonicotinoid insecticide exposures in two agrarian regions of Cameroon, the South-West region and Littoral region. The study involved 188 men, including 125 farmers and 63 nonfarmers. Spot urine samples were obtained from these subjects and subjected to liquid chromatographic-tandem mass spectrometric analysis for concentrations of neonicotinoid compounds, including acetamiprid, clothianidin, dinotefuran, imidacloprid, thiacloprid, nitenpyram, thiamethoxam, and N-dm-acetamiprid. Neonicotinoid compounds were detected in all study participants, and residues of all the screened pesticides were detected among participants. N-dm-Acetamiprid and imidacloprid were the most prevalent among the subjects (100.0% and 93.1%, respectively), whereas nitenpyram was less common (3.2%). The median values of imidacloprid and total urinary neonicotinoid concentrations were elevated among farmers (0.258 vs. 0.126 µg/L and 0.829 vs. 0.312 µg/L, respectively). Altogether the findings showed that both the farmer and nonfarmer study populations of Cameroon were exposed to multiple residues of neonicotinoids, with relatively higher levels of pesticides generally recorded among farmers. Although exposure levels of the neonicotinoids were generally lower than their respective reference doses, these results warrant further research on the health risk evaluation of multiple residues of the pesticides and reinforcement of control measures to minimize the exposure risks, especially among farmers. Environ Toxicol Chem 2024;43:952-964. © 2024 SETAC.

Association between Chronic Environmental Lead (Pb) Exposure and Cytokines in Males and Females of Reproductive Age from Kabwe, Zambia.

Lead (Pb) poisoning remains a great public health challenge globally known to induce a wide range of ailments in both children and adults. The current study investigated the association of chronic environmental Pb exposure and immunomodulatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8) in adult males and females living in Kabwe, Zambia. The standard human cytokine/chemokine Milliplex assay was used to quantify plasma cytokines from four groups categorized as low (<10 µg/dL) and high (>10 µg/dL) blood lead level (BLL) groups, namely, low BLL female (n = 47; BLL = 3.76 µg/dL), low BLL Male (n = 43; BLL = 4.13 µg/dL), high BLL female (n = 21; BLL = 23.5 µg/dL), and high BLL male (n = 18; BLL = 23.7 µg/dL), respectively. The low BLL group was associated with increased TNF-α levels, and the high BLL group was associated with reduced TNF-α levels in female subjects. No associations between BLL and the levels of IL-8 and TNF-α cytokines were observed in either females or males, respectively. A negative correlation between BLL and TNF-α was found in female subjects, suggesting that an increase in BLL accompanied by a reduction in TNF-α. The reduced levels of circulating TNF-α in female subjects suggest that chronic Pb exposure could predispose females to immune and inflammation-related disorders than their male counterparts. Further studies are recommended to ascertain the impact of chronic Pb exposure on immunomodulatory cytokines, especially in females.

Biological effects related to exposure to polychlorinated biphenyl (PCB) and decabromodiphenyl ether (BDE-209) on cats.

As an animal familiar to humans, cats are considered to be sensitive to chemicals; cats may be exposed to polychlorinated biphenyls (PCBs) and decabromodiphenyl ether (BDE-209) from indoor dust, household products, and common pet food, leading to adverse endocrine effects, such as thyroid hormone dysfunction. To elucidate the general biological effects resulting from exposure of cats to PCBs and PBDEs, cats were treated with a single i.p. dose of a principal mixture of 12 PCBs and observed for a short-term period. Results revealed that the testis weight, serum albumin, and total protein of the treated group decrease statistically in comparison with those in the control group. The negative correlations suggested that the decrease in the total protein and albumin levels may be disturbed by 4'OH-CB18, 3'OH-CB28 and 3OH-CB101. Meanwhile, the serum albumin level and relative brain weight decreased significantly for cats subjected to 1-year continuous oral administration of BDE-209 in comparison to those of control cats. In addition, the subcutaneous fat as well as serum high-density lipoprotein (HDL) and triglycerides (TG) levels increased in cats treated with BDE-209 and down-regulation of stearoyl-CoA desaturase mRNA expression in the liver occurred. These results suggested that chronic BDE-209 treatment may restrain lipolysis in the liver, which is associated with lipogenesis in the subcutaneous fat. Evidence of liver and kidney cell damage was not observed as there was no significant difference in the liver enzymes, blood urea nitrogen and creatinine levels between the two groups of both experiments. To the best of our knowledge, this is the first study that provides information on the biochemical effects of organohalogen compounds in cats. Further investigations on risk assessment and other potential health effects of PCBs and PBDEs on the reproductive system, brain, and lipid metabolism in cats are required.

Human Health Risk Assessment from Lead Exposure through Consumption of Raw Cow Milk from Free-Range Cattle Reared in the Vicinity of a Lead-Zinc Mine in Kabwe.

Lead (Pb) contamination in the environment affects both humans and animals. Chronic exposure to Pb via dietary intake of animal products such as milk from contaminated areas poses a health risk to consumers; therefore, the present study investigated Pb contamination in cow milk and its health risk impact on humans through consumption of milk from cattle reared in the proximity of a Pb−Zn mine in Kabwe, Zambia. Fresh milk samples were collected from cows from Kang'omba (KN), Kafulamse (KF), Mpima (MP), Mukobeko (MK), and Munga (MN) farming areas. Pb determination was performed using Graphite Flame Absorption Atomic Spectrophotometry (GFAAS). Cow milk Pb levels showed different concentration patterns according to season, distance, and location of the farms from the Pb−Zn mine. The overall mean Pb levels were ranged 0.60−2.22 µg/kg and 0.50−4.24 µg/kg in the wet and dry seasons, respectively. The mean Pb concentration, chronic daily intake (CDIs), target hazard quotients (THQs), and incremental lifetime cancer risk (ILCR) results obtained were all within the permissible limits of 20 µg/kg, 3 and 12.5 µg/kg-BW/day, <1 and 10−4 to10−6, respectively. In conclusion, although Pb was detected in milk from cows reared in Kabwe, the health risk effects of Pb exposure associated with the consumption of milk in both adults and children were negligible.

Environmentally relevant lead (Pb) water concentration induce toxicity in zebrafish (Danio rerio) larvae.

Early developmental stages of aquatic organisms including fish are inherently vulnerable to lead (Pb) and other water metal contaminants. However, reports on the deleterious effects of environmentally relevant Pb levels are limited. To this end, we exposed 2.5 h post fertilization (hpf) old zebrafish (Danio rerio) embryos to a range of Pb concentrations encompassing environmentally relevant levels (1, 10, 25, 50 and 100 µg/L Pb) until 96 hpf. Exposure negatively impacted the development and survival of zebrafish embryos by inducing embryo coagulation related mortalities in a concentration-dependent manner. At 24 hpf, the highest level of exposure (100 µg/L Pb) had impaired embryo activity characterized by reduced burst activity and the number of movements per minute made by embryos. At 72 hpf, newly hatched larvae exhibited adverse cardiovascular effects (100 µg/L Pb group) and neuromuscular effects (50 and 100 µg/L Pb groups). The antioxidant system dysregulation evidenced by downregulation of catalase, and upregulation of mRNA expression of glutathione S-transferase and cytochrome oxidase subunit I were observed. The pro-apoptotic tumour protein P53 (TP53) and the anti-apoptotic B cell lymphoma -2 (Bcl-2) mRNA expression levels were also affected. The former was downregulated across exposed groups and the latter was upregulated and downregulated in the groups with Pb concentrations less than 50 µg/L Pb and downregulated in 50 µg/L Pb, respectively. These findings suggest that Pb within environmentally relevant levels may be deleterious to developing zebrafish.

Glutathione S-transferase gene polymorphisms in association with susceptibility to lead toxicity in lead- and cadmium-exposed children near an abandoned lead-zinc mining area in Kabwe, Zambia.

Interindividual genetic variations determine human's susceptibility to heavy metal-induced toxicity. Thus, we analyzed blood concentrations of lead (Pb) and cadmium (Cd) in 140 lead-exposed children. Genotyping of the glutathione S-transferase (GST) genes, GSTM1, GSTT1, and GSTP1 genes, was carried out to investigate their possible association with heavy metal concentrations and the risk of susceptibility to Pb toxicity. Exposure to both heavy metals was prevalent among the children. The blood Pb level ranged from 3.30 to 74.0 µg dL-1 with an average value of 26.8 µg dL-1 that is five times above its reference level. The average Cd level (0.22 µg L-1) was below its reference level. The metal-gene interaction showed positive correlation between GSTT1 null genotype and Pb and Cd levels (ß = 0.11; p = 0.02 and ß = 0.10; p = 0.01, respectively). More pronounced effects (ß = 0.19; p < 0.01 and ß = 0.25; p = 0.04) were found for the mixture of the three putative genes with blood Pb concentration. The susceptibility analysis using 10 µg dL-1 as blood Pb cutoff level showed a high risk of Pb toxicity (OR = 2.54; 95% CI: 1.02-6.32, p = 0.04) for children carrying the GSTP1 Ile/Val genotype. Further, the combined effect of GSTP1 Ile/Val with GSTT1 null genotype was more pronounced and showed an increased risk of susceptibility to Pb toxicity (OR = 11.7; 95% CI: 1.36-102.1, p = 0.02). In summary, this study suggests that GSTT1 null and GSTP1 Ile/Val genotypes are the main genetic factors, and individual and specific combinations of GSTP1 Ile/Val with GSTM1 and GSTT1 GST polymorphisms are associated with susceptibility to Pb toxicity.

Urinary concentrations of neonicotinoid insecticides were related to renal tubular dysfunction and neuropsychological complaints in Dry-zone of Sri Lanka.

Neonicotinoids are systemic insecticides used since the 1990's , that possess renal tubular toxicity. We conducted a field-based descriptive study in the North Central Dry-zone of Sri Lanka, where chronic kidney disease (CKD) of unknown etiology has been increasing since the 1990's. To elucidate the relationship between renal tubular dysfunctions and urinary neonicotinoids concentrations, we collected spot urine samples from15 CKD patients, 15 family members, and 62 neighbors in 2015, analyzed two renal tubular biomarkers, Cystatin-C and L-FABP, quantified seven neonicotinoids and a metabolite N-desmethyl-acetamiprid by LC-MS/MS; and we investigated their symptoms using a questionnaire. Cystatin-C and L-FABP had a positive correlation (p < 0.001). N-Desmethyl-acetamiprid was detected in 92.4% of the urine samples, followed by dinotefuran (17.4%), thiamethoxam (17.4%), clothianidin (9.8%), thiacloprid and imidacloprid. Dinotefuran and thiacloprid have never been registered in Sri Lanka. In High Cystatin-C group (> 70 µg/gCre, n = 7), higher urinary concentration of dinotefuran (p = 0.009), and in Zero Cystatin-C group (< LOQ, n = 7), higher N-desmethyl-acetamiprid (p = 0.013), dinotefuran (p = 0.049), and thiacloprid (p = 0.035), and more complaints of chest pains, stomachache, skin eruption and diarrhea (p < 0.05) were found than in Normal Cystatin-C group (n = 78). Urinary neonicotinoids may be one of the potential risk factors for renal tubular dysfunction in this area.

Bioaccumulation of DDT and other organochlorine pesticides in amphibians from two conservation areas within malaria risk regions of South Africa.

The threat to wildlife from chemical exposure exists regardless of the presence of conservation boundaries. An issue exacerbated by the use of environmentally persistent insecticides for vector control and long-range transport of legacy persistent organic pollutants. In this comparative study between two important conservation regions in South Africa, Kruger National Park (KNP) and Ndumo Game Reserve (NGR), we assessed organochlorine pesticide (OCP) accumulation in several anuran species collected from within the conservation regions. The two conservation regions differ in size and subsequent proximity of collection sites to OCP input sources. Detectable concentrations of OCPs were present in ∼ half the frogs analysed from KNP and ∼all frogs from NGR and total OCP loads were similar between regions, where measured in the same species. The OCP profiles in KNP frogs were representative of legacy pesticides likely introduced via long-range transport, whereas NGR profiles showed influence of current use of DDT consistent with close proximity to sources. This indicates amphibians can accumulate OCPs within conservation regions and that the exposure of non-target organisms inside conservation regions to current use pesticides has a strong association with proximity to sources. These results serve to inform conservation management decision making with regard to the non-target organism effects of chemical interventions such as vector control pesticide use in and around conservation regions.

Analysis of lead distribution in avian organs by LA-ICP-MS: Study of experimentally lead-exposed ducks and kites.

Lead poisoning of wild birds by ingestion of lead ammunition occurs worldwide. Histopathological changes in organs of lead-intoxicated birds are widely known, and lead concentration of each organ is measurable using mass spectrometry. However, detailed lead localization at the suborgan level has remained elusive in lead-exposed birds. Here we investigated the detailed lead localization in organs of experimentally lead-exposed ducks and kites by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). In both the ducks and kites, lead accumulated diffusely in the liver, renal cortex, and brain. Lead accumulation was restricted to the red pulp in the spleen. With regard to species differences in lead distribution patterns, it is noteworthy that intensive lead accumulation was observed in the arterial walls only in the kites. In addition, the distribution of copper in the brain was altered in the lead-exposed ducks. Thus, the present study shows suborgan lead distribution in lead-exposed birds and its differences between avian species for the first time. These findings will provide fundamental information to understand the cellular processes of lead poisoning and the mechanisms of species differences in susceptibility to lead exposure.

Urinary free metanephrines measurement in dogs with adrenal gland diseases using a new simple liquid chromatography tandem mass spectrometry method.

Measurement of urinary metanephrines in spot samples is used for the diagnosis of canine pheochromocytoma (PC). We describe a simple analytical method based on liquid chromatography tandem mass spectrometry (LC-MS/MS) for measuring free metanephrine (MN) and normetanephrine (NMN) in spot urine samples. Using the developed method, we evaluated the stability of urinary free-MN and free-NMN at various storing conditions. In addition, we assessed the feasibility of urinary free-MN and -NMN measurement for diagnosing PC. Urine samples were mixed with stable isotope internal standards and thereafter purified by ultrafiltration. The purified samples were analyzed by LC-MS/MS in the multiple reaction monitoring mode after separation on a multimode octa decyl silyl column. The coefficient of variation of free-MN and -NMN measurement was 7.6% and 5.5%, respectively. The linearity range was 0.5-10 µg/l for both analytes. Degradation was less than 10% for both analytes under any of the storage conditions. The median free-NMN ratio to creatinine of 9 PC dogs (595, range 144-47,961) was significantly higher (P<0.05) than that of 13 dogs with hypercortisolism (125, range 52-224) or 15 healthy dogs (85, range 50-117). The developed method is simple and may not require acidification of spot urine. The results of this preliminary retrospective study suggest that the measurement of urinary free metanephrines is a promising tool for diagnosing canine PC.

An Investigation of the Wild Rat Crown Incisor as an Indicator of Lead (Pb) Exposure Using Inductively Couple Plasma Mass Spectrometry (ICP-MS) and Laser Ablation ICP-MS.

Lead (Pb) is a metal toxicant of great public health concern. The present study investigated the applicability of the rat incisor in Pb exposure screening. The levels of lead in teeth (Pb-T) in the crown and root of incisors in laboratory Pb-exposed Sprague Dawley rats were quantified using inductively coupled plasma mass spectrometry (ICP-MS). The crown accumulated much Pb-T than the root of the Sprague Dawley rat incisor. The levels of lead in blood (Pb-B) were positively correlated with the Pb-T in the crown and root incisors of the Sprague Dawley rats. As an application of the Pb-T crown results in experimental rats, we subsequently analyzed the Pb-T in the crown incisors of Pb-exposed wild rats (Rattus rattus) sampled from residential sites within varying distances from an abandoned lead-zinc mine. The Pb-T accumulation in the crown of incisors of R. rattus rats decreased with increased distance away from the Pb-Zn mine. Furthermore, the Pb-T was strongly correlated (r = 0.85) with the Pb levels in the blood. Laser ablation ICP-MS Pb-T mappings revealed a homogenous distribution of Pb in the incisor with an increased intensity of Pb-T localized in the tip of the incisor crown bearing an enamel surface in both Sprague Dawley and R. rattus rats. These findings suggest that Pb-T in the crown incisor may be reflective of the rat's environmental habitat, thus a possible indicator of Pb exposure.

Chronic low-dose exposure to imidacloprid potentiates high fat diet-mediated liver steatosis in C57BL/6J male mice.

Hepatic steatosis is known to precede a continuum of events that lead to hepatic metabolic dysfunction, inflammation and carcinogenesis. Recently, studies have linked xenobiotic exposures to hepatic steatogenesis and its associated metabolic disorders; however, the underlying mechanisms remain elusive. This study aimed to elucidate the mechanistic role of imidacloprid in the prevalence of high fat diet (HFD)-induced liver steatosis, using a C57BL/6J mice model. Mice (3 weeks old) were fed with HFD and treated with 0.6 mg/kg bw/day (one-tenth of the NOAEL) of imidacloprid through water or diet, for 24 weeks. In a controlled group, mice were fed with only HFD. At the end of the study, imidacloprid treatment significantly potentiated HFD-induced body weight gain in mice. Also, imidacloprid increased the liver weights of mice, with complimentary reductions in mesenteric and gonadal white adipose tissue weights. Histopathological analysis of liver revealed a drastic steatosis in imidacloprid treated mice. Following a real-time qPCR analysis, imidacloprid upregulated transcriptions of hepatic fatty acid biosynthesis-related transcription factors and genes. Imidacloprid also induced hepatic expression of the gene encoding pregnane X receptor; but had no significant effect on hepatic expressions of liver X receptor and aryl hydrocarbon receptor. The imidacloprid treatment further enhanced serum alanine aminotransferase levels but downregulated hepatic antioxidant mRNA expressions. Ultimately, this study suggested an imidacloprid-potentiation effects on prevalence of HFD-induced liver steatosis via transcriptional modulations of the hepatic FA biosynthesis pathway.

Levels of DDTs and other organochlorine pesticides in healthy wild Nile crocodiles (Crocodylus niloticus) from a flagship conservation area.

Mass Nile crocodile (Crocodylus niloticus) deaths in Africa's premier conservation area, the Kruger National Park (KNP), prompted numerous studies to determine possible causes of the sudden die-offs. The majority highlighted the involvement of the anthropocene to crocodile mass mortalities. One of the potential causative agents was identified as legacy compounds such as organochlorine pesticides (OCPs) present in the various aquatic ecosystems of the KNP. Thus, this study aimed to quantify OCP levels in wild crocodiles from the aquatic systems associated with the KNP. As part of a larger study, muscle tissue samples were collected from tails of 12 wild crocodiles. Results indicated that eight of the 19 OCPs analysed for were quantifiable. These included DDTs (2130-167968 ng/g lw), chlordanes (BD - 7583 ng/g lw) and cyclodeines (BD - 872 ng/g lw). Measured concentrations indicated spatial- and sex-related differences in accumulation patterns. DDT and its metabolites, paricularly p,p'-DDE accumulated to the highest concentrations of the OCP groups. Levels of the different groups of OCPs were the highest recorded in recent history from any crocodilian tissue. The different measured OCP residues were between 2.5 and 120 times higher than levels reported in literature, depending on the compound. These results are of ecotoxicological significance and have several management implications. In view of individuals being sampled from a conservation area it emphasizes the fact that pollutants know no boundaries and that premier conservation areas such as the world renowned KNP may be some of the most contaminated areas of the world.

Clinical biochemical parameters associated with the exposure to multiple environmental metals in residents from Kabwe, Zambia.

Lead (Pb) interferes with various bodily functions. Although high blood Pb (Pb-B) levels in residents from Kabwe, Zambia have been reported, the accumulation pattern of other metals remains unknown. The study was designed to determine the Pb-B, blood cadmium (Cd-B), and zinc (Zn-B) values of 504 representative samples from Kabwe, as well as the potential associated adverse health effects. The Pb-B level ranged from 0.79 to 154.75 µg/dL and generally increased in areas near the mine. A significant elevation of Cd-B was observed in two areas (0.37 ± 0.26 and 0.32 ± 0.30 µg/L) where the two highest mean Pb-B levels were recorded. By contrast, the Zn-B values did not differ greatly with respect to area. Some blood biochemical parameters relating to hepatic and renal functions were out of the normal range in approximately 20-50% of studied adult participants. The δ-aminolevulinic acid dehydratase (δ-ALAD) activity was significantly inhibited in the two areas contaminated by Pb and Cd. A significant negative relationship was observed between metal levels and clinical parameters, e.g., between Pb-B and δ-ALAD for all the age categories and between Cd-B and the estimated glomerular filtration rate for all the age categories except 0-4 years. The elevated Cd-B in areas near the mine relative to the other areas suggested the potential adverse health effects of Cd and/or the interaction of Pb and Cd. A significant association of metal levels with clinical parameters also indicated the effects of metal exposure on hematopoietic, hepatic, and renal systems.

Lead, Zinc and Cadmium Accumulation, and Associated Health Risks, in Maize Grown near the Kabwe Mine in Zambia in Response to Organic and Inorganic Soil Amendments.

Health risks due to heavy metal (HM) contamination is of global concern. Despite concerns of high levels of HMs in soils near Kabwe mine in Zambia, edible crop production is common, posing potential health risks. This study assessed the potential of chicken manure (CM), triple superphosphate (TSP) and a blended fertilizer (BF; consisting of Nitrogen, Phosphorous and Potassium (NPK) fertilizer and composted chicken manure) to reduce lead (Pb), zinc (Zn) and cadmium (Cd) in soils and their accumulation in maize grown near the Kabwe mine. Maize was grown to maturity and its HM concentrations and associated health risk indices were calculated. All soil amendments decreased bioavailable soil Pb concentrations by 29-36%, but only CM decreased Zn, while the amendments increased or had no effect on Cd concentrations compared to the control. The amendments reduced Pb (>25%) and Zn concentrations (>18%) in the maize stover and grain. However, Cd concentrations in maize grain increased in the BF and TSP treatments. Bioaccumulation factors showed that Cd had the highest mobility from the soil into maize stover and grain, indicating the need for greater attention on Cd in Kabwe despite its apparently lower soil concentration compared to Pb and Zn. The hazard quotients for Pb and Cd were much greater than one, indicating a high risk of possible exposure to toxic levels by people consuming maize grain grown in this area. This study demonstrated the significant potential of manure and phosphate-based amendments to reduce Pb and Zn, and to some extent Cd, uptake in maize grain and consequently reduce associated health risks.

Altered hepatic cytochrome P450 expression in cats after chronic exposure to decabromodiphenyl ether (BDE-209).

The knowledge of cytochrome P450 (CYP) expression involved in chemical exposure are necessary in clinical applications for the medication and prediction of adverse effects. The aim of this study was to evaluate the mRNA expression of CYP1-CYP3 families in cats exposed to BDE-209 for one year. All selected CYP isoforms showed no significant difference in mRNA expressions between control and exposure groups, however, CYP3A12 and CYP3A131 revealed tend to be two times higher in the exposure group compared to control group. The present results indicate that the chronic exposure of BDE209 could not alter CYP expression in the liver of cats. This result considered caused by the deficiency of CYP2B subfamily which is major metabolism enzyme of polybrominated diphenyl ethers (PBDEs) in cat.

Bioimaging of Pb and STIM1 in mice liver, kidney and brain using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) and immunohistochemistry.

Lead (Pb) pollution is one of the most serious environmental problems and has attracted worldwide attention. Pb causes hematological, central nervous system, as well as renal toxicity, and so on. Although many investigations about Pb in blood to evaluate pollution status and toxic effects have been reported, there are open question about biological behavior of Pb. In order to reveal any toxicological mechanisms or influences, we focused on the local distribution of Pb in mice organs. Lead acetate (100 mg/L and 1000 mg/L) in drinking water were given to the BALB/c mice (male, seven weeks of age, N = 24) for three weeks. Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) analysis revealed a homogenous distribution of Pb in the liver and inhomogeneous distribution in the kidney and brain. The hippocampus, thalamus, and hypothalamus had higher concentrations than other areas such as the white matter. Surprisingly, in the kidney, Pb tended to accumulate in the medulla rather than the cortex, strongly suggesting that high sensitivity areas and high accumulation areas differ. Moreover, distribution of stromal interacting protein 1 (STIM1) which is candidate gene of Pb pathway to the cells was homogenous in the liver and kidney whereas inhomogeneous in the brain. In contrast to our hypothesis, interestingly, Pb exposure under the current condition did not induce mRNA expressions for any candidate channel or transporter genes. Thus, further study should be conducted to elucidate the local distribution of Pb and other toxic metals, and pathway that Pb takes to the cells.

Effects of the organochlorine p,p'-DDT on MCF-7 cells: Investigating metabolic and immune modulatory transcriptomic changes.

The organochlorine pesticide dichloro-diphenyl-trichloroethane (DDT) is persistent in the environment and leads to adverse human health effects. High levels in breast milk pose a threat to both breast tissue and nursing infants. The objectives of this study were to investigate DDT-induced transcriptomic alterations in enzymes and transporters involved in xenobiotic metabolism, immune responses, oxidative stress markers, and cell growth in a human breast cancer cell line. MCF-7 cells were exposed to both environmentally-relevant and previously-tested concentrations of p,p'-DDT in a short-term experiment. Significant up-regulation of metabolizing enzymes and transporters (ACHE, GSTO1, NQO1 and ABCC2) and oxidative stress markers (CXCL8, HMOX-1, NFE2L2 and TNF) was clearly observed. Conversely, UGT1A6, AHR and cell growth genes (FGF2 and VEGFA) were severely down-regulated. Identification of these genes helps to identify mechanisms of p,p'-DDT action within cells and may be considered as useful biomarkers for exposure to DDT contamination.

Characterization, Spatial Variation and Risk Assessment of Heavy Metals and a Metalloid in Surface Soils in Obuasi, Ghana.

BACKGROUND: Soil contamination with heavy metals and metalloids has become an increasingly important issue in recent years. OBJECTIVES: The present study examines possible contamination of the environment with metals from gold mining activities in Obuasi, Ghana. METHODS: Soil samples were collected from commercial and residential areas and tailing dams in Obuasi in order to investigate the extent of lead (Pb), cadmium (Cd), mercury (Hg), copper (Cu), zinc (Zn), cobalt (Co), chromium (Cr), nickel (Ni) and arsenic (As) pollution, create thematic maps showing the extent of heavy metals pollution, identify the sources of pollution, and to assess risks to humans and the surrounding ecological system. RESULTS: Mean concentrations of metals from the study were found in the order of As > Cu > Zn > Cr > Ni > Pb > Co > Hg > Cd. The results showed that all communities were severely polluted with As, and distribution maps highlighted two hot spots at the sulfite treatment plant and Pompura treatment plant tailings dams. Additionally, the levels of Pb, Cu and Zn were elevated around the city center where vehicular traffic is very dense. Principal component analysis indicated that mining activities may have significantly contributed to metal levels in Obuasi soils. The potential ecological risk (RI) indicated that soils in 41% of the communities pose very high risks to the surrounding ecological system, 50% pose considerable risk, and 9% pose a moderate risk. Arsenic and Hg contributed 73 and 15% of the RI, respectively. The average hazard quotient due to soil As exposure was 2.51 ± 1.23 and ingestion of soils in 95% of the communities in the study area could pose non-carcinogenic health risks to children. Moreover, the average cancer risk for children from the communities was 1.13 × 10-3. Based on the United States Environmental Protection Agency (USEPA) recommendation for cancer risk of 10-6 to 10-4, the cancer risk for children (> 10-3) was higher in 45% of the studied communities. CONCLUSIONS: The central part of the study area is polluted with Pb, Zn and Cu, and As pollution is severe in all of the studied communities. The RI from all study sites revealed very high risk to the ecological system, including mammals. There could be non-cancer and cancer risks to Obuasi residents due to ingestion of As-contaminated soils, and children are particularly vulnerable. COMPETING INTERESTS: The author declares no competing financial interests.

Molecular and functional characterization of UDP-glucuronosyltransferase 1A in cynomolgus macaques.

UDP-glucuronosyltransferases (UGTs) are drug-metabolizing enzymes essential for the metabolism of endogenous substrates and xenobiotics. Molecular characteristics of UGTs have been extensively investigated in humans, but in cynomolgus macaques, a non-human primate species widely used in drug metabolism studies, remain to be investigated. In this study, 12 UGT1A cDNAs (UGT1A1, 1A2, 1A4A, 1A4B, 1A5A, 1A5B, 1A5C, 1A6, 1A7, 1A8, 1A9, and 1A10) were isolated and characterized in cynomolgus macaques. UGT1A5C cDNA did not contain a complete coding region due to nonsense mutations, and was excluded from further analysis. Amino acid sequences of all 11 cynomolgus UGT1As had high sequence identities (92-95%) with human UGT1As and were phylogenetically close to human UGT1As. These cynomolgus UGT1A genes shared exons 2-5, and contained a variable exon 1 unique to each gene, similar to human UGT1A genes. Moreover, cynomolgus and human UGT1A gene clusters were located in corresponding regions in the genome. Among the 10 tissue types analyzed, cynomolgus UGT1A mRNAs were most abundantly expressed in the liver, jejunum, and/or kidney, the drug-metabolizing organs, similar to human UGT1As. Among these 11 cynomolgus UGT1A mRNAs, cynomolgus UGT1A2, UGT1A9, and UGT1A10 mRNAs were most abundantly expressed in the liver, kidney, and jejunum, respectively. Cynomolgus liver microsomes and UGT1A proteins catalyzed glucuronidation of the substrates human UGT1As catalyze, including 4-methylumbelliferone, 4-nitrophenol, estradiol, trifluoperazine, serotonin, and propofol, although trifluoperazine glucuronidation was not catalyzed by any cynomolgus UGT1A proteins. These results suggest that cynomolgus UGT1As are functional enzymes with molecular similarities to human UGT1As.