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Transcriptomic and proteomic insights into patulin mycotoxin-induced cancer-like phenotypes in normal intestinal epithelial cells

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Abstract

Patulin (PAT) is a natural contaminant of fruits (primarily apples) and their products. Significantly, high levels of contamination have been found in fruit juices all over the world. Several in vitro studies have demonstrated PAT’s ability to alter intestinal structure and function. However, in real life, the probability of low dose long-term exposure to PAT to humans is significantly higher through contaminated food items. Thus, in the present study, we have exposed normal intestinal cells to non-toxic levels of PAT for 16 weeks and observed that PAT had the ability to cause cancer-like properties in normal intestinal epithelial cells after chronic exposure. Here, our results showed that chronic exposure to low doses of PAT caused enhanced proliferation, migration and invasion ability, and the capability to grow in soft agar (anchorage independence). Moreover, an in vivo study showed the appearance of colonic aberrant crypt foci (ACFs) in PAT-exposed Wistar rats, which are well, establish markers for early colon cancer. Furthermore, as these neoplastic changes are consequences of alterations at the molecular level, here, we combined next-generation RNA sequencing with liquid chromatography mass spectrometry-based proteomic analysis to investigate the possible underlying mechanisms involved in PAT-induced neoplastic changes.

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Acknowledgements

Authors are grateful to the Director, CSIR-Indian Institute of Toxicology Research, Lucknow. NS acknowledged the Department of Biotechnology for fellowship. This work was financially supported by Science and Engineering Research Board, Department of Science and Technology, Government of India (SERB No. EMR/2015/000983). The authors have declared no conflict of interest. The manuscript is CSIR-IITR communication #3705.

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Authors and Affiliations

  1. Food Toxicology Laboratory, Food, Drug, and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India

    Neha Singh, Indra Dev, Saurabh Pal & Kausar Mahmood Ansari

  2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India

    Neha Singh, Indra Dev, Saurabh Pal, Sanjeev Kumar Yadav, Mohammed M. Idris & Kausar Mahmood Ansari

  3. Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, 226001, Uttar Pradesh, India

    Sanjeev Kumar Yadav

  4. CSIR-Centre for Cellular and Molecular Biology, Hyderabad, 500007, Telangana, India

    Mohammed M. Idris

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  1. Neha Singh
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Singh, N., Dev, I., Pal, S. et al. Transcriptomic and proteomic insights into patulin mycotoxin-induced cancer-like phenotypes in normal intestinal epithelial cells. Mol Cell Biochem 477, 1405–1416 (2022). https://doi.org/10.1007/s11010-022-04387-3

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