Biomarqueurs d'évaluation d'une exposition envionnementale complexe : évaluation de l'exposition des égoutiers aux substances génotoxiques., Biomarkers of evaluation of complex environmental exposure : exposure assessment of sewage workers to genotoxicants

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Publié par

Sous la direction de Denis Zmirou-Navier, Luc Ferrari
Thèse soutenue le 25 mars 2010: Nancy 1
Les égoutiers sont exposés à une grande variété de mélanges de produits chimiques beaucoup ce sont des substances génotoxiques ou cancérigènes. Le but de cette étude transversale était d'explorer des biomarqueurs intégrés d’exposition et des effets précoces chez les égoutiers afin de mieux apprécier leur risque cancérogène (article I-protocole). L'article II expose l'étape de validation préalable effectuée sur la lignée cellulaire pour nos objectifs. Avec un recueil en 10 mois et sur une base hebdomadaire, nous avons, a) évalué l'exposition personnelle des égoutiers (n=34) et administratifs (n=30) (groupe témoin) à des hydrocarbures aromatiques polycycliques (HAP) et composés organiques volatils (COV) dans l'air des lieux de travail, b) évalué la génotoxicité de leurs extraits organiques urinaire par des tests in vitro : tests des comète et des micronoyaux sur les cellules Hep G2, c) évalué la réponse à un stress oxydatif de l'ADN par la mesure du 8 oxo 2' deoxyguanosine urinaire (8 oxodG) dans les urines de 24h (Article III). Les tests ont montré la présence de plus de génotoxiques dans les urines des égoutiers (P <0,001). La moyenne du 8 oxodG urinaire chez les égoutiers était plus élevée (non significatif, P = 0,28) que les administratifs et ses valeurs moyennes ont été associées (P = 0,04) avec les années de travail dans le système des égouts. Les concentrations des HAP et COV dans l'atmosphère professionnelle des égoutiers étaient élevées par rapport à celles des administratifs (P <0,01) et il a été montré une augmentation de risque du cancer en utilisant les facteurs d'équivalence de toxicité et de risque unitaire de cancer. En conclusion, les biomarqueurs intégrés urinaire d’exposition et non spécifiques montrent que les égoutiers sont professionnellement exposés aux mélanges des substances génotoxiques. Il n’est pas possible de relier nos résultats avec l’accroissement du risque cancérogène chez les égoutiers.
-8 oxodG
-Biomarqueurs
-Test de comète et de micronoyau
-ADN stress oxydatif
-Génotoxicité
-HAP
-Egoutiers
-COV
Sewage workers are exposed to a wide variety of mixtures of chemicals many were shown to be genotoxicants or carcinogens. The aim of this cross sectional study was to explore integrated biomarkers of exposure and of early effects among sewage workers in order to better assess their carcinogenic risk (Paper I-protocol). Paper II, describes the validation step performed prior to choose the cellular line that meet our objectives. Over 10 months and on weekly basis, we, a) assessed the personal exposure of sewage (n=34) and office (n=30) workers (control group) to polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) in the air of workplaces, b) evaluated the genotoxicity of organic urine extracts by in vitro comet and micronucleus assays on Hep G2 cells, c) assessed the DNA oxidative stress by the 24h urinary 8 oxo 2' deoxyguanosine (8 oxodG) (Paper III). The tests showed greater genotoxicity in the urine extracts of sewage workers (P<0.001). The 24hr urinary 8 oxodG mean level in sewage workers was higher (nonsignificant, P=0.28) than office workers and its mean values were associated (P=0.04) with working years in sewage system. Workplace air concentrations of PAHs and VOCs were elevated in sewage compared to office workplaces (P<0.01) and resulted in an increased lifetime cancer risk using toxicity equivalent factors and inhalation unit risk of cancer. In conclusion, the applied integrated and non-specific urinary biomarkers show that sewage workers experience exposure to multiple genotoxicants at the workplace. It is not possible to simply link our results with the increased cancer risk in sewage workers.
Source: http://www.theses.fr/2010NAN10008/document
Publié le : vendredi 28 octobre 2011
Lecture(s) : 95
Nombre de pages : 303
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➢ Contact SCD Nancy 1 : theses.sciences@scd.uhp-nancy.fr




LIENS


Code de la Propriété Intellectuelle. articles L 122. 4
Code de la Propriété Intellectuelle. articles L 335.2- L 335.10
http://www.cfcopies.com/V2/leg/leg_droi.php
http://www.culture.gouv.fr/culture/infos-pratiques/droits/protection.htm Nancy-Université
'\ .Université~enri Poincaré


UFR de Médecine
Ecole Doctorale BioSE (Biologie-Santé-Environnement)

Thèse
Présentée et soutenue publiquement pour l’obtention du titre de
DOCTEUR DE L’UNIVERSITE HENRI POINCARE
Mention : Sciences de la Vie et de la Santé

par Hamzeh ALZABADI

Biomarkers of Evaluation of Complex Environmental Exposure:

Exposure Assessment of Sewage Workers to Genotoxicants


Le 25 Mars 2010
Membres du jury :
Professeur, Université Catholique de Louvain, Rapporteurs : Monsieur Alfred BERNARD
Louvain
Professeur, Université de la Méditerranée, Monsieur Alain BOTTA
Marseille
Examinateurs : Madame Nuha EL SHARIF Professeur, AL-Quds Université, Jérusalem
Professeur, Nancy Université, Université Henri Monsieur Denis ZMIROU-NAVIER Poincaré, Directeur de thèse
Professeur, Nancy Université, Université Henri Monsieur Christophe PARIS Poincaré
Maître de conférences HDR, Nancy Université,
Monsieur Luc FERRARI
Université Henri Poincaré, Co-directeur de thèse
Professeur, Nancy Université, Université Henri
Membre invité : Monsieur Jean-Yves LE DEAUT Poincaré
…………………………………………………………………………………….
UMR_S 954, INSERM UHP Nutrition Génétique et Exposition aux Risques
Environnementaux. Faculté de Médecine - 9 avenue de la Forêt de Haye - BP. 184
54505 Vandœuvre-Lès-Nancy Cedex France.
ii I Know Why the Caged Bird Sings



A free bird leaps on the back of the wind
and floats downstream till the current ends
and dips his wing in the orange suns rays and dares to claim the sky.

But a bird that stalks down his narrow cage
can seldom see through his bars of rage
his wings are clipped and his feet are tied so he opens his throat to sing.

The caged bird sings with a fearful trill
of things unknown but longed for still
and his tune is heard on the distant hill
for the caged bird sings of freedom.

The free bird thinks of another breeze
and the trade winds soft through the sighing trees
and the fat worms waiting on a dawn bright lawn and he names the sky his own.

But a caged bird stands on the grave of dreams
his shadow shouts on a nightmare scream
his wings are clipped and his feet are tied so he opens his throat to sing.







Maya Angelou (1928-Present)
iii iv Dedication






To my dear mother and father,

To my sisters and brothers,



To my wife “Reham”,

To my son “Tejan”,

You are always in my heart,










Hamzeh ALZABADI
v vi Acknowledgements
I would like to gratefully acknowledge the enthusiastic supervision and direction of
Professor Denis ZMIROU-NAVIER during this work. Not only the valuable scientific qualities, but also his
human quality, were the spirit for me to finalize this work. He helped whenever I was in need. Meeting and
working with him were the best things that ever could have happened to me in France. He has provided for an
excellent scientific environment in the Unit of INSERM-U954. I would like also to express my sincere thanks
and appreciation to Doctor Luc FERRARI, the Co-director of this thesis, for his guidance and counsel during
this work. I appreciate the intellectual exchange you have both provided during this thesis.
To the member of the jury-Professor Alain BOTTA, Professor Alfred BERNARD,
Professor Nuha EL SHARIF, and Professor Christophe PARIS, I am grateful for the precious time you all
devoted, the advice and valuable criticism of this work which revealed many valuable points for the
development of this work and bring this thesis into presentable version. To the member of the jury Monsieur le
Professeur et le Député de Meurthe et Moselle-Jean-Yves Le DEAUT, I appreciate the time you devoted for
this scientific work, but also your human solidarity and help when I was in need.
I am grateful to all members of our Unit and to my friends in our laboratory, for being the surrogate family
during the years I stayed in France and for their continued moral support. From the staff, Chantal FAYE for
the technical support and for learning me the comet and micronucleus assays. Aline BERTHELIN is especially
thanked for her care and attention and help in thesis editing.
I acknowledge the financial support I received from the French Foreign Ministry, Prix Whitney, the Medical
School of Nancy-1 University, and INSERM. This work was mainly granted by the Region Lorraine and the
French National Institute of Cancer “INCa”. I would like also to express my gratitude to all those who have
shared their knowledge and technical expertise with me or have helped in questionnaires preparations and
development, preparing the protocols, training and performing the field work: The team of Doctor Aziz
TIBERGUENT in the services of Occupational and Preventive Medicine of the town of Paris; the team of
Mr. Yvon Le Moullec in the Laboratory of Hygiene of the Town of Paris (LHVP).
I would like also to thank all the participants in these studies for their cooperation, understanding, and the
time they gave all over the fieldwork.
Finally, I am forever indebted to my parents, sister and brothers who supported me throughout this entire
thesis and without whom their love this work would not have been fulfilled. I am also indebted to my wife
“Reham” for her love, understanding, endless patience, support, help and encouragement when it was most
required, but also for giving us our son “Tejan” during this thesis.
I may have forgotten to acknowledge others who have offered assistance and support during this work. Such
oversight does not indicate any lack of gratitude.
vii viii Table of contents
Dedication ............................................................................................................................................. V
Acknowledgements ............................ VII
Table of contents .................................................................................................................................. IX
List of figures ..... XII
List of tables ...... XIII
List of tables ...................................................................................................................................... XIII
List of appendices ............................. XIV
Abbreviations ...... XV

1. Introduction ........................................................................................................................... 1
1.1. Background ............................. 1
1.2. Health hazards in the workplace of sewage workers .............................. 3
1.2.1. Biological and physical hazards ................................................................ 3
1.2.2. Chemical hazard ...................................................... 3
1.3. Characterization of exposure among sewage workers ............................ 4
1.3.1. Sewage drains indoor air pollution ......................................................................................... 5
1.3.1.1. Polycyclic aromatic hydrocarbons (PAHs) ............. 6
1.3.1.2. Volatile organic compounds (VOCs) ...................... 6
1.3.2. Other exposures in sewage system (skin contact and ingestion) ............................................ 7
1.4. Health effects among sewage workers .................................................... 7
1.4.1. Morbidity studies ................................ 8
1.4.2. Mortality and cancer studies ................................................................................................... 8
1.5. Biomarkers of exposure to genotoxicants ............. 10
1.5.1. In vitro comet assay .............................................................................................................. 10
1.5.1.1. History and definition ........... 10
1.5.1.2. General principle of the assay ............................................................................................... 11
1.5.1.3. Fields of application .............................................................................................................. 11
1.5.2. In vitro micronucleus assay ... 12
1.5.2.1. History and definition ........... 13
1.5.2.2. General principle of the assay ............................................................................................... 14
1.5.2.3. Fields of application .............................................................................................................. 15
1.5.3. Comet and micronucleus assays in vitro human occupational studies .. 16
1.6. Biomarkers of early effects of genotoxicants ........ 18
1.6.1. The 24h urinary 8-oxodG ...................................................................................................... 18
1.6.2. DNA-adducts ........................................................ 19
ix

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