I work with development and application of in vitro bioassays to study how chemicals can interact with molecular targets leading to adverse outcomes in organisms. The established methods are of relevance for risk assessment of environmental pollutants both for human health and for animal health.
Overview of research area
I work with the development and application of methods based on the 21st century toxicology-strategy to perform effect-directed analysis of environmental samples or to screen single compounds for bioactivity.
21st century toxicology – a new era in toxicity testing
Traditional animal toxicity testing has been challenged in this century to shift towards toxicity pathway-based approaches for a more efficient evaluation of large number of chemicals and a better understanding of the mechanisms behind toxicological effects. The toxicity pathway describes what is happening in a cell when it is exposed to a toxic substance. This includes the molecular interaction between the chemical and the biological target, and the cellular defense mechanisms triggered by the toxic substance. This strategy is often referred to as 21st century toxicology. Cell-based in vitro assays are of great value for studies of toxicity pathways. These in vitro models enables us to measure the initial molecular effects of a low-dose exposure of a chemical on the biological system, which can be used for prediction of toxicity, rather than more proximal end-points after often unrealistic high-dose exposure, which are used in regulatory animal studies.
Pollutants in water – an environmental and health problem of great concern
Environmental pollutant contamination is an emerging problem in the context of both drinking water and field water. Field water is contaminated by e.g. pesticides, industrial chemicals, pharmaceutical products, and chemicals from consumer products. The problems with environmental pollutants in water is addressed in four different national environmental quality objectives; a non-toxic environment, good-quality groundwater, flourishing lakes and streams, and a balanced marine environment and flourishing coastal areas and archipelagos. Today, most environmental monitoring of drinking water and environmental water is conducted by chemical analysis. This strategy has major disadvantages; it is expensive and time consuming, it can only detect known substances, it does not necessarily correlate to toxic effects, and it is very difficult to assess mixture effects. Our research aims to establish a battery of new test methods that would allow us to assess the total toxic activity in a large number of water samples to a moderate cost.
Effect-directed analysis is based on the idea that the biological effect of an environmental sample is a trigger for further chemical analysis. If a certain sample lack toxic potential, the need for chemical characterization of that sample is low. If a sample on the other hand exert toxicity, it is prioritized to use integrated chemical and toxicological profiling of the sample to understand which compound(s) that are causing the toxicity. Effect-directed analysis can also be used to identify previously unknown toxic compounds, preferably by fractionation of the sample and integrated chemical and toxicological profiling of the fraction(s) that carries the toxic potential, including non-targeted chemical analysis. The principle of effect-directed analysis shows great promise for future environmental monitoring efforts and the field is rapidly expanding internationally.
Swedish Research Council (Vetenskapsrådet), Research Council Formas, Swedish Fund for Research Without Animal Experiments, The Royal Swedish Academy of Agriculture and Forestry, SLU Environmental Monitoring programme Non-toxic Environment.
Publikationer i urval
Lungu-Mitea S, Oskarsson A, Lundqvist J. (2018) Development of an oxidative stress in vitro assay in zebrafish (Danio rerio) cell lines. Scientific Reports 8:12380
Rosenmai AK, Lundqvist J, Le Godec T, Ohlsson Å, Tröger R, Hellman B, Oskarsson A. (2018) In vitro bioanalysis of drinking water from source to tap. Accepted for publication in Water Research (accepted April 4, 2018) DOI: 10.1016/j.watres.2018.04.009
Niss F, Rosenmai AK, Mandava G, Örn S, Oskarsson A, Lundqvist J. (2018) Toxicity bioassays with concentrated cell culture media - a methodology to overcome the chemical loss by conventional preparation of water samples. Accepted for publication in Environmental Science and Pollution Research (accepted February 28, 2018). DOI: 10.1007/s11356-018-1656-4
Rosenmai AK, Niss F, Mandava G, Lundqvist J, Oskarsson A. (2018) Impact of natural organic matter in water on in vitro bioactivity assays. Chemosphere 200:209-216
Rosenmai AK, Ahrens L, Le Godec T, Lundqvist J, Oskarsson A. (2018) Relationship between PPARα activity and cellular concentration of 14 perfluoroalkyl substances in HepG2 cells. Journal of Applied Toxicology 38:219-226.
Lundqvist J, Kirkegaard T, Laenkholm A-V, Duun-Henriksen AK, Bak M, Feldman D, Lykkesfeldt AE. (2018) Williams syndrome transcription factor (WSTF) acts as an activator of estrogen receptor signaling in breast cancer cells and the effect can be abrogated by 1α,25-dihydroxyvitamin D3. Journal of Steroid Biochemistry and Molecular Biology 177:171-178
Lundqvist J, Tringali C, Oskarsson A. (2017) Resveratrol, piceatannol and analogs inhibit activation of both wild-type and T877A mutant androgen receptor. Journal of Steroid Biochemistry and Molecular Biology 174:161-168.
Lundqvist J, Pekar H, Oskarsson A. (2017) Microcystins activate nuclear factor erythroid 2-related factor 2 (Nrf2) in human liver cells in vitro - Implications for an oxidative stress induction by microcystins. Toxicon 126:47-50
Norlin M, Lundqvist J, Ellfolk M, Hellström Pigg M, Gustafsson J, Wikvall K. (2017) Drug-mediated gene regulation of vitamin D3 metabolism in primary human dermal fibroblasts. Basic Clin Pharmacol Toxicol 120(1):59-63
Lundqvist J, Hellman B, Oskarsson A. (2016) Fungicide prochloraz induces oxidative stress
and DNA damage in vitro. Food and Chemical Toxicology 91:36–41
Iskov Kopp T, Lundqvist J, Kofoed Petersen R, Nellemann C, Oskarsson A, Kristiansen K, Vogel U. (2015) An in vitro PPARγ activity-based screening of chemicals for breast carcinogens. Human and Experimental Toxicology 34(11):1106-18
Hole S, Pedersen AM, Hansen SK, Lundqvist J, Yde CW, Lykkesfeldt AE. (2015) New cell culture model for aromatase inhibitor-resistant breast cancer shows sensitivity to fulvestrant treatment and cross-resistance between letrozole and exemestane. Int J Oncol 46(4):1481-90
Lundqvist J, Yde CW, Lykkesfeldt AE. (2014) 1a,25-Dihydroxyvitamin D3 inhibits NFkB signaling in anti-estrogen sensitive and resistant breast cancer cells. Steroids 85:30-35
Swami S, Krishnan A, Peng L, Lundqvist J, Feldman D. (2013) Calcitriol represses estrogen receptor expression in breast cancer cells via two negative vitamin D response elements. Endocrine-Related Cancer 20:565-577
Lundqvist J, Hansen SK, Lykkesfeldt AE. (2013) Vitamin D analog EB1089 inhibits aromatase expression by dissociation of comodulator WSTF from the CYP19A1 promoter – a new regulatory pathway for aromatase. Biochim Biophys Acta Molecular Cell Research 1833:40–47
Lundqvist J, Wikvall K, Norlin M. (2012) Vitamin D-mediated regulation of CYP21A2 transcription – a novel mechanism for vitamin D action. Biochim Biophys Acta General Subjects 1820:1553-1559
Lundqvist J, Norlin M (2012) Effects of CYP7B1-related steroids on androgen receptor activation in different cell lines. Biochim Biophys Acta Molecular and Cell Biology of Lipids 1821:973-979
Fex Svenningsen A, Wicher G, Lundqvist J, Pettersson H, Corell M, Norlin M. (2011) Effects on DHEA levels by estrogen in rat astrocytes and CNS co-cultures via the regulation of CYP7B1-mediated metabolism. Neurochemistry International 58:620-624
Lundqvist J, Norlin M, Wikvall K. (2011) 1a,25-Dihydroxyvitamin D3 exerts tissue-specific effects on estrogen and androgen metabolism. Biochim Biophys Acta Molecular and Cell Biology of Lipids 1811:263-270.
Pettersson H, Lundqvist J, Norlin M. (2010) Effects of CYP7B1-mediated catalysis on estrogen receptor activation. Biochim Biophys Acta Molecular and Cell Biology of Lipids 1801:1090-1097.
Lundqvist J, Norlin M, Wikvall K. (2010) 1a,25-Dihydroxyvitamin D3 affects hormone production and expression of steroidogenic enzymes in human adrenocortical NCI-H295R cells. Biochim Biophys Acta Molecular and Cell Biology of Lipids 1801:1056-1062.
Pettersson H, Lundqvist J, Oliw E, Norlin M. (2009) CYP7B1-mediated metabolism of 5alpha-androstane-3alpha,17beta-diol (3alpha-Adiol): a novel pathway for potential regulation of the cellular levels of androgens and neurosteroids. Biochim Biophys Acta Molecular and Cell Biology of Lipids 1791:1206-1215.