Barbara Tudek received her doctoral degree in 1983 from the Warsaw Medical University, Poland. After her PhD studies she went to Ludwig Institute for Cancer Research, Toronto, Canada, as a postdoc, followed by a stay at the Institute Gustave Roussy, Villejuif, France. She subsequently returned to Poland and joined the Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw where she established her independent research group and obtained professorship in 2006. In 2012 she joined the Institute of Genetics and Biotechnology, Faculty of Biology, Warsaw University as an academic professor. She was an active member of EEMGS for almost 40 years and a President of the Polish EEMGS Section for 10 years, from 2002 till 2012. She organized two annual EEMGS meetings in Warsaw, Poland in 2002 and 2012.
Her early studies were devoted to the genotoxic properties of various food and petroleum derived compounds, such as furfural, thiram, nitrofurans, flavonoids and other carcinogens. As an independent researcher she focused on the study of the mechanisms of removal of DNA lesions arising from oxidation and alkylation.
Oxidative stress is a source of multiple DNA lesions. In human cells damaged bases such as 8-oxoguanine are removed from the DNA chain by the Base Excision Repair or by the phosphohydrolase hMTH1 from the free nucleotide pool. Her research group in collaboration with the group of Prof. R. Oliński from Bydgoszcz University determined the differential efficiency of 8oxoG removal in healthy versus colon and lung cancer patients. These studies suggested that the levels of 8-oxoG and DNA repair enzymes can be used as a prognostic of long-term patient survival and pointed to the need to develop compounds that would block DNA damage pathways in hopes to increase the efficiency of existing anti-cancer therapies.
Much of her independent work focused on the study of the metabolism and mutagenic capacity of oxidized derivatives of polyunsaturated fatty acids such as acrolein, croton and 4-hydroxy-2-nonenal (HNE). These compound can produce simple DNA adducts such as ε-adenine and ε-cytosine, which have high miscoding capacity, or larger propano adducts and DNA crosslinks, which induce transcription arrest, recombination and chromosomal aberrations.
Etheno adducts are removed by the Base Excision Repair system. Her group determined that, as in the case of 8-oxoG, the efficiency of removal of εA and εC differs in the leukocytes of lung and colon cancer patients versus healthy controls and found significant alterations in the efficiency of lesion repair in the healthy versus tumor tissue. It was suggested that alteration to the efficiency of DNA repair can drive carcinogenesis into a specific histopathological type. These studies also showed that treatment of cells with alkylating agents increased their sensitivity to oxidative and methylating agents, hence showing that different mutagenic compounds, when acting together, can have synergistic effects.
Many of her studies pointed to a link between ageing and the efficiency of DNA removal. Large HNE-derived crosslinks to DNA are removed by the Xpf/ERCC1 system. In collaboration with the group of Prof. L. Niederhofer she showed that mice deficient in ERCC1 function show accelerated ageing when fed with a diet rich in polyunsaturated fatty acids. HNE can also produce adducts to proteins and her group has underlined the negative impact of large HNE concentrations on the function of CSA/B protein, involved in initiation of Co-transcriptional DNA repair (TCR) and WRN helicase, responsible for maintaining DNA integrity. Mutations in CSB and WRN lead to development of the Cockayne and Werner syndromes both of which result in accelerated ageing.
Prof. Barbara Tudek studies pointed to the importance of individual differences in DNA damage removal efficiency to both carcinogenesis and potentially ageing. She has also underlined the versatile effects of mutagen impact on DNA and protein integrity depending on the concentration or co-occurrence of different damaging compounds. Her studies contributed to deeper understanding the DNA damage removal mechanisms and gave incentives for improvement of cancer diagnostics and anti-cancer therapies.
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