Project acronym CHIPS
Project Effects of Prenatal Exposure to Acrylamide on Health: Prospective Biomarker-Based Studies
Researcher (PI) Marie Pedersen
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), LS7, ERC-2017-STG
Summary Background: Acrylamide is a chemical formed in many commonly consumed foods and beverages. It is neurotoxic, crosses the placenta and has been associated with restriction of fetal growth in humans. In animals, acrylamide causes heritable mutations, tumors, developmental toxicity, reduced fertility and impaired growth. Therefore, the discovery of acrylamide in food in 2002 raised concern about human health effects worldwide. Still, epidemiological studies are limited and effects on health of prenatal exposure have never been evaluated.
Research gaps: Epidemiological studies have mostly addressed exposure during adulthood, focused on cancer risk in adults, and relied on questionnaires entailing a high degree of exposure misclassification. Biomarker studies on prenatal exposure to acrylamide from diet are critically needed to improve exposure assessment and to determine whether acrylamide leads to major diseases later in life.
Own results: I have first authored a prospective European study showing that prenatal exposure to acrylamide, estimated by measuring hemoglobin adducts in cord blood, was associated with fetal growth restriction, for the first time.
Objectives: To determine the effects of prenatal exposure to acrylamide alone and in combination with other potentially toxic adduct-forming exposures on the health of children and young adults.
Methods: Both well-established and innovative biomarker methods will be used for characterization of prenatal exposure to acrylamide and related toxicants in blood from pregnant women and their offspring in prospective cohort studies with long-term follow-up. Risk of neurological disorders, impaired cognition, disturbed reproductive function and metabolic outcomes such as obesity and diabetes will be evaluated.
Perspectives: CHIPS project will provide a better understanding of the impact of prenatal exposure to acrylamide from diet on human health urgently needed for targeted strategies for the protection of the health.
Summary
Background: Acrylamide is a chemical formed in many commonly consumed foods and beverages. It is neurotoxic, crosses the placenta and has been associated with restriction of fetal growth in humans. In animals, acrylamide causes heritable mutations, tumors, developmental toxicity, reduced fertility and impaired growth. Therefore, the discovery of acrylamide in food in 2002 raised concern about human health effects worldwide. Still, epidemiological studies are limited and effects on health of prenatal exposure have never been evaluated.
Research gaps: Epidemiological studies have mostly addressed exposure during adulthood, focused on cancer risk in adults, and relied on questionnaires entailing a high degree of exposure misclassification. Biomarker studies on prenatal exposure to acrylamide from diet are critically needed to improve exposure assessment and to determine whether acrylamide leads to major diseases later in life.
Own results: I have first authored a prospective European study showing that prenatal exposure to acrylamide, estimated by measuring hemoglobin adducts in cord blood, was associated with fetal growth restriction, for the first time.
Objectives: To determine the effects of prenatal exposure to acrylamide alone and in combination with other potentially toxic adduct-forming exposures on the health of children and young adults.
Methods: Both well-established and innovative biomarker methods will be used for characterization of prenatal exposure to acrylamide and related toxicants in blood from pregnant women and their offspring in prospective cohort studies with long-term follow-up. Risk of neurological disorders, impaired cognition, disturbed reproductive function and metabolic outcomes such as obesity and diabetes will be evaluated.
Perspectives: CHIPS project will provide a better understanding of the impact of prenatal exposure to acrylamide from diet on human health urgently needed for targeted strategies for the protection of the health.
Max ERC Funding
1 499 531 €
Duration
Start date: 2018-07-01, End date: 2023-06-30
Project acronym ToMeTuM
Project Towards the Understanding a Metal-Tumour-Metabolism
Researcher (PI) Vojtech Adam
Host Institution (HI) VYSOKE UCENI TECHNICKE V BRNE
Call Details Starting Grant (StG), LS7, ERC-2017-STG
Summary A tumour cell uses both genetic and protein weapons in its development. Gaining a greater understanding of these lethal mechanisms is a key step towards developing novel and more effective treatments. Because the metal ion metabolism of a tumour cell is not fully understood, we will address the challenge of explaining the mechanisms of how a tumour cell copes both with essential metal ions and platinum based drugs. The metal-based mechanisms help a tumour to grow on one side and to protect itself against commonly used metal-based drugs. On the other side, the exact description of these mechanisms, which are being associated with multi-drug resistance occurrence and failure of a treatment, still remains unclear. We will reveal the mechanism of the as yet not understood biochemical and molecularly-biological relationships and correlations between metal ions and proteins in a tumour development revealing the way how to suppress the growth and development of a tumour and to markedly enhance the effectiveness of a treatment.
To achieve this goal, we will focus on metallothionein and its interactions with essential metals and metal-containing anticancer drugs (cisplatin, carboplatin, and oxaliplatin). Their actions will be monitored both in vitro and in vivo. For this purpose, we will optimize electrochemical, mass spectrometric and immune-based methods. Based on processing of data obtained, new carcinogenetic pathways will be sought on cell level and proved by genetic modifications of target genes. The discovered processes and the pathways found will then be tested on two animal experimental models mice bearing breast tumours (MCF-7 and 4T1) and MeLiM minipigs bearing melanomas.
The precise description of the tumour related pathways coping with metal ions based on metallothioneins will direct new highly effective treatment strategies. Moreover, the discovery of new carcinogenetic pathways will open a window for understanding of cancer formation and development.
Summary
A tumour cell uses both genetic and protein weapons in its development. Gaining a greater understanding of these lethal mechanisms is a key step towards developing novel and more effective treatments. Because the metal ion metabolism of a tumour cell is not fully understood, we will address the challenge of explaining the mechanisms of how a tumour cell copes both with essential metal ions and platinum based drugs. The metal-based mechanisms help a tumour to grow on one side and to protect itself against commonly used metal-based drugs. On the other side, the exact description of these mechanisms, which are being associated with multi-drug resistance occurrence and failure of a treatment, still remains unclear. We will reveal the mechanism of the as yet not understood biochemical and molecularly-biological relationships and correlations between metal ions and proteins in a tumour development revealing the way how to suppress the growth and development of a tumour and to markedly enhance the effectiveness of a treatment.
To achieve this goal, we will focus on metallothionein and its interactions with essential metals and metal-containing anticancer drugs (cisplatin, carboplatin, and oxaliplatin). Their actions will be monitored both in vitro and in vivo. For this purpose, we will optimize electrochemical, mass spectrometric and immune-based methods. Based on processing of data obtained, new carcinogenetic pathways will be sought on cell level and proved by genetic modifications of target genes. The discovered processes and the pathways found will then be tested on two animal experimental models mice bearing breast tumours (MCF-7 and 4T1) and MeLiM minipigs bearing melanomas.
The precise description of the tumour related pathways coping with metal ions based on metallothioneins will direct new highly effective treatment strategies. Moreover, the discovery of new carcinogenetic pathways will open a window for understanding of cancer formation and development.
Max ERC Funding
1 377 495 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
