Genetic Toxicology

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Description

Project leader: Björn Hellman

In our studies, we are focusing on primary DNA damage in the form of DNA strand breaks using the Comet assay. With this assay, single and double strand breaks are detected in individual cells. We have further developed the protocol by streamlining laboratory-, and data processing procedures. Our method development has so far resulted in papers describing a protocol for what we call the Flash-comet (Bivehed et al., 2020; Bivehed & Hellman, 2020) and we have also described an alternative statistical approach (UCDAS) for the analysis of comet data (Bivehed et al., 2020). In collaboration with Professor Ola Söderberg's research group, we are currently developing a method that makes it possible to distinguish between single and double strand breaks in one and the same "comet tail". In another collaborative project with the Ångström laboratory, we will hopefully soon have a more automated version of Flash-comet. In addition to the Comet assay, we have also set up a cytochalasin B-based micronucleus test to detect chromosome damage in single cells. The group currently consists of professor Björn Hellman, PhD student Erik Bivehed and research assistant Rein Fadoul.

The major objective is to improve the risk assessment when it comes to human exposures to genotoxic agents. When exposed to carcinogens, it is important to distinguish between genotoxic carcinogens and substances that increase the risk of cancer by acting via other mechanisms. DNA damage can, for example, occur when a substance directly attacks DNA, but it can also occur as a result of, for example, cytotoxicity – which for a genetic toxicologist is less serious issue. Nowadays we mainly work with cultured cells to identify genotoxic substances and in our projects on method development. Previously we have used primary DNA damage in peripheral lymphocytes as biological exposure markers using blood samples from patients who have received chemotherapy or from those exposed to radon in the home environment. In other previous projects, we established long-term cultures of lymphocytes from blood donors to, among other things, study individual variation in sensitivity to genotoxic agents, DNA repair, oxidative DNA damage, etc.

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• H. Vaghef & B. Hellman. Demonstration of chlorobenzene-induced DNA damage in mouse lymphocytes using the single cell gel electrophoresis assay. Toxicology 96, 19-28.

• H. Vaghef, P. Nygren, C. Edling, J. Bergh & Björn Hellman (1997). Alkaline single cell gel electrophoresis and human biomonitoring for genotoxicity: a pilot study on breast cancer patients undergoing chemotherapy including cyclophosphamide, Mutation Research, 395, 127-138.

• M. Andersson, E. Agurell, H. Vaghef, G. Bolcsfoldi & B. Hellman (2003). Extended-term cultures of human T-lymphocytes and the comet assay: a useful combination when testing for genotoxicity in vitro? Mutation Research, 540, 43-55.

• M. A. Andersson, K. V. Peterson-Grawé, O. M. Karlsson, L. A. G. Abramsson-Zetterberg & B. E. Hellman (2007). Evaluation of the potential genotoxicity of chromium picolinate in mammalian cells in vivo and in vitro. Food & Chemical Toxicoogy, 45, 1097-1106.

• J. Demma, K. Hallberg & B. Hellman (2009). Genotoxicity of plumbagin and its effects on catechol and NQNO-induced DNA damage in mouse lymphoma cells.Toxicology In Vitro, 23, 266-271.

• R. Åsgård, S. Hagdoost, S. Osterman Golkar, B. Hellman & S. Czene (2013). Evidence for different mechanisms of action behind the mutagenic effects of 4-NOPD and OPD: the role of DNA damage, oxidative stress and an imbalanced nucleotide pool. Mutagenesis 28, 637-644.

• E. Bivehed, A. Gustafsson, A. Berglund & B. Hellman (2020). Evaluation of potential DNA damaging effects of nitenpyram and imidacloprid in human U937-cells using a new statistical approach to analyse comet data. Exposure and Health 12, 547-554. DOI: 10.1007/s12403-019-00328-6.

• E. Bivehed, O. Söderberg and B. Hellman (2020). Flash-comet: Significantly improved speed and sensitivity of the comet assay through the introduction of lithium-based solutions and a more gentle lysis. Mutation Research (2020). Doi: 10.1016/j.mrgentox.2020.503240.

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