maternal cadmium exposure during pregnancy and fetal development

1
Abstracts / Toxicology Letters 211S (2012) S43–S216 S143 Cd + 20 mg Zn + 10 mg Cu + 40 mg Mg/kg b.w./day. After digestion with concentrated nitric and perchloric acids, Cd, Zn, Cu and Mg content was measured by atomic absorption spectrometry. Co-treatment with Zn + Cu + Mg had beneficial effect on renal Cd content: a significant decrease (more than 50%) in kidney Cd content was observed in animals supplemented with bioelements if compared with Cd group. However, supplementation with Zn, Cu and Mg caused decrease of bioelements itself if compared to Cd intoxicated animals and even significantly lowered levels of Cu and Mg in kidney if compared with controls. Although co-treatment with Zn, Cu and Mg caused positive effects on Cd content its effect on bioelements is a matter of concern. Nevertheless, these find- ings could be explained by rather high doses of administrated bioelements and their interactions on the level of absorption from gastrointestinal tract. doi:10.1016/j.toxlet.2012.03.521 P22-10 Maternal cadmium exposure during pregnancy and fetal development Maria Kippler 1 , Fahmida Tofail 2 , Yukiko Wagatsuma 3 , Renee Gardner 1 , Jena Hamadani 2 , Anisur Rahman 2 , Marie Vahter 1 1 Karolinska Institutet, Stockholm, Sweden, 2 icddr,b, Dhaka, Bangladesh, 3 Univeristy of Tsukuba, Tsukuba, Japan Purpose: The toxic metal cadmium (Cd), commonly occurring in food, is embryotoxic and teratogenic in several animal species, but data in humans is limited. The aim of our ongoing study is to assess potential effects of maternal Cd exposure during pregnancy on fetal development. Methods: This prospective cohort study was nested into a population-based supplementation trial in pregnancy, conducted in rural Bangladesh. We selected all pregnant women recruited February 2002–January 2003, with singleton births and measure- ments of birth size (weight, length, head- and chest circumference; n = 1616). Fetal growth parameters were measured at gestational week 14 and 30 using ultrasound. Maternal urinary Cd (a long- term exposure biomarker) at gestational week 8 was measured with ICPMS. Results and conclusion: Multivariable-adjusted linear regression analyses showed that maternal urinary Cd (median 0.63 g/L) was negatively associated with birth weight and head circumference. Stratification by sex showed that the negative associations were mainly restricted to girls, with little evidence in boys. For girls, an increment of 1 g/L Cd in maternal urine was associated with a decrease in head- and chest circumference by 0.26 and 0.24 cm, respectively and in birth weight by 45 g. Multivariable-adjusted quantile regression showed that Cd similarly affected girls of dif- ferent sizes. Ultrasound data indicated associations with head measures, femur length and abdominal circumference in early ges- tation. In conclusion, we found a sex-specific association between maternal Cd exposure and fetal development, mainly in girls, requiring further mechanistic studies. We are currently assessing the potential link with neurodevelopment in childhood. doi:10.1016/j.toxlet.2012.03.522 P22-12 Toxic metal and essential trace element levels of Turkish Blood donors Tülin Soylemezoglu 1 , Ismail Akinci 1 , Vugar Aliyev 1 , Zeliha Kayaalti 1 , Engin Tutkun 2 1 Ankara University, Turkey, 2 Ankara Occupational Diseases Hospital, Turkey The aim of this study is to determine the level of toxic met- als, Cd and Pb and trace elements, Fe, Zn and Cu in blood of healthy unexposed Turkish subjects living in Ankara and to determine indi- viduals living in our country if they are at risk for chronic metal toxicity. Pb and Cd levels were analyzed by graphite furnace atomic absorbtion spectrometry, Fe, Cu and Zn levels were analyzed by flame atomic absorbtion spectrometry. These analyses performed in the blood of 211 male blood donors (age ranging from 19 to 55, mean ages of 33.71 ± 8.69 years). SPSS version 16.0 software for Windows was used for the all statistical analysis. The average levels of Cd, Pb, Fe, Zn and Cu were 1.27 ± 0.88 ppb, 25.13 ± 12.44 ppb 4.84 ± 0.79 ppm, 1.10 ± 0.21 ppm, 476.53 ± 42.41 ppm, respectively. When the correlation coef- ficients were calculated with among the ages-metal levels and body mass index (BMI)-metal levels, the statistically significant positive correlation was found between the only age and Cu levels (p < 0.01), the other metals were not (p > 0.05). There were not any significant correlation between the BMI and all measured metal levels (p > 0.05). Also, the association was assessed between the cigarette smoking and metal levels in the blood samples of blood donor volunteers and highly statistically significant association was determined between the cigarette smoking and Cd levels (p < 0.001). These results may provide toxicologists and clinical chemists about these toxic metals and trace elements in order to determine whether people have trace element deficiencies or have been exposed to higher metal levels. doi:10.1016/j.toxlet.2012.03.523 P22-13 Metals induce cytochrome P4501A1 through inhibition of metabolic degradation of FICZ Afshin Mohammadi Bardbori 1 , Emma Wincent 2 , Ulf Rannug 3 , Agneta Rannug 1 1 Karolinska Institutet, Sweden, 2 Karolinska Institutet and Stockholm Univ, Sweden, 3 Stockholm University, Sweden Metals seem to have the capacity to activate the aryl hydro- carbon receptor (AHR). The objective of this study was to investigate whether the metals arsenic, mercury, cadmium and nickel activate the AHR indirectly by interfering with the metabolic degradation of the tryptophan-derived high affinity AHR ligand 6- formylindolo[3,2-b]carbazole (FICZ). Transcriptional activation of cytochrome P4501A1 (CYP1A1) was estimated with a luciferase reporter assay using human hep- atoma HepG2-derived HepG2-XRE-Luc cells, and CYP1A1 enzyme activity was analyzed in immortalized human keratinocytes (HaCaT) with 7-ethoxyresorufin as a substrate (EROD assay). To test the ability of the chosen metals to activate the AHR in the absence of the natural ligand FICZ, all cell treatments were performed in commercial DMEM medium as well as in DMEM medium prepared

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Page 1: Maternal cadmium exposure during pregnancy and fetal development

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Abstracts / Toxicology L

d + 20 mg Zn + 10 mg Cu + 40 mg Mg/kg b.w./day. After digestionith concentrated nitric and perchloric acids, Cd, Zn, Cu and Mg

ontent was measured by atomic absorption spectrometry.Co-treatment with Zn + Cu + Mg had beneficial effect on renal

d content: a significant decrease (more than 50%) in kidney Cdontent was observed in animals supplemented with bioelementsf compared with Cd group. However, supplementation with Zn,u and Mg caused decrease of bioelements itself if compared tod intoxicated animals and even significantly lowered levels of Cund Mg in kidney if compared with controls. Although co-treatmentith Zn, Cu and Mg caused positive effects on Cd content its effect

n bioelements is a matter of concern. Nevertheless, these find-ngs could be explained by rather high doses of administratedioelements and their interactions on the level of absorption fromastrointestinal tract.

oi:10.1016/j.toxlet.2012.03.521

22-10aternal cadmium exposure during pregnancy and fetal

evelopment

aria Kippler 1, Fahmida Tofail 2, Yukiko Wagatsuma 3, Reneeardner 1, Jena Hamadani 2, Anisur Rahman 2, Marie Vahter 1

Karolinska Institutet, Stockholm, Sweden, 2 icddr,b, Dhaka,angladesh, 3 Univeristy of Tsukuba, Tsukuba, Japan

Purpose: The toxic metal cadmium (Cd), commonly occurring inood, is embryotoxic and teratogenic in several animal species, butata in humans is limited. The aim of our ongoing study is to assessotential effects of maternal Cd exposure during pregnancy on fetalevelopment.

Methods: This prospective cohort study was nested into aopulation-based supplementation trial in pregnancy, conducted

n rural Bangladesh. We selected all pregnant women recruitedebruary 2002–January 2003, with singleton births and measure-ents of birth size (weight, length, head- and chest circumference;= 1616). Fetal growth parameters were measured at gestationaleek 14 and 30 using ultrasound. Maternal urinary Cd (a long-

erm exposure biomarker) at gestational week 8 was measuredith ICPMS.

Results and conclusion: Multivariable-adjusted linear regressionnalyses showed that maternal urinary Cd (median 0.63 �g/L) wasegatively associated with birth weight and head circumference.tratification by sex showed that the negative associations wereainly restricted to girls, with little evidence in boys. For girls, an

ncrement of 1 �g/L Cd in maternal urine was associated with aecrease in head- and chest circumference by 0.26 and 0.24 cm,espectively and in birth weight by 45 g. Multivariable-adjusteduantile regression showed that Cd similarly affected girls of dif-erent sizes. Ultrasound data indicated associations with head

easures, femur length and abdominal circumference in early ges-ation. In conclusion, we found a sex-specific association between

aternal Cd exposure and fetal development, mainly in girls,

equiring further mechanistic studies. We are currently assessinghe potential link with neurodevelopment in childhood.

oi:10.1016/j.toxlet.2012.03.522

211S (2012) S43–S216 S143

P22-12Toxic metal and essential trace element levels of Turkish Blooddonors

Tülin Soylemezoglu 1, Ismail Akinci 1, Vugar Aliyev 1, ZelihaKayaalti 1, Engin Tutkun 2

1 Ankara University, Turkey, 2 Ankara Occupational DiseasesHospital, Turkey

The aim of this study is to determine the level of toxic met-als, Cd and Pb and trace elements, Fe, Zn and Cu in blood of healthyunexposed Turkish subjects living in Ankara and to determine indi-viduals living in our country if they are at risk for chronic metaltoxicity.

Pb and Cd levels were analyzed by graphite furnace atomicabsorbtion spectrometry, Fe, Cu and Zn levels were analyzed byflame atomic absorbtion spectrometry. These analyses performedin the blood of 211 male blood donors (age ranging from 19 to 55,mean ages of 33.71 ± 8.69 years). SPSS version 16.0 software forWindows was used for the all statistical analysis.

The average levels of Cd, Pb, Fe, Zn and Cu were 1.27 ± 0.88 ppb,25.13 ± 12.44 ppb 4.84 ± 0.79 ppm, 1.10 ± 0.21 ppm,476.53 ± 42.41 ppm, respectively. When the correlation coef-ficients were calculated with among the ages-metal levels andbody mass index (BMI)-metal levels, the statistically significantpositive correlation was found between the only age and Cu levels(p < 0.01), the other metals were not (p > 0.05). There were not anysignificant correlation between the BMI and all measured metallevels (p > 0.05). Also, the association was assessed between thecigarette smoking and metal levels in the blood samples of blooddonor volunteers and highly statistically significant associationwas determined between the cigarette smoking and Cd levels(p < 0.001). These results may provide toxicologists and clinicalchemists about these toxic metals and trace elements in order todetermine whether people have trace element deficiencies or havebeen exposed to higher metal levels.

doi:10.1016/j.toxlet.2012.03.523

P22-13Metals induce cytochrome P4501A1 through inhibition ofmetabolic degradation of FICZ

Afshin Mohammadi Bardbori 1, Emma Wincent 2, Ulf Rannug 3,Agneta Rannug 1

1 Karolinska Institutet, Sweden, 2 Karolinska Institutet and StockholmUniv, Sweden, 3 Stockholm University, Sweden

Metals seem to have the capacity to activate the aryl hydro-carbon receptor (AHR). The objective of this study was toinvestigate whether the metals arsenic, mercury, cadmium andnickel activate the AHR indirectly by interfering with the metabolicdegradation of the tryptophan-derived high affinity AHR ligand 6-formylindolo[3,2-b]carbazole (FICZ).

Transcriptional activation of cytochrome P4501A1 (CYP1A1)was estimated with a luciferase reporter assay using human hep-atoma HepG2-derived HepG2-XRE-Luc cells, and CYP1A1 enzymeactivity was analyzed in immortalized human keratinocytes(HaCaT) with 7-ethoxyresorufin as a substrate (EROD assay). To test

the ability of the chosen metals to activate the AHR in the absenceof the natural ligand FICZ, all cell treatments were performed incommercial DMEM medium as well as in DMEM medium prepared