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ISSN Печать: 0731-8898
ISSN Онлайн: 2162-6537
Indexed in
Molecular Characterization of Isocyanate-Induced Male Germ-Line Genomic Instability
Краткое описание
Male reproductive health is exquisitely sensitive to environmental insults as evidenced by the rising incidence of testicular cancers and low and probably declining semen quality. Isocyanates, such as methyl isocyanate (MIC), with their wide industrial applications, are known to exert severe ill health effects. The present study was performed to find out the pathophysiological implications of isocyanate exposure on the male germ line. The investigations were performed in the cultured mouse spermatogonial GC-1 spg cell line using N-succinimidyl N-methylcarbamate, a surrogate chemical to MIC. DNA damage, oxidative stress and apoptosis response parameters increased with time of exposure and dose after treatment. Treated cells also displayed elevated levels of inflammatory cytokines as well as morphological transformation and stress-responsive senescence. Chromosomal aberrations, telomere anomaly, aneuploidy and variable amplification of microsatellite repeats additionally indicated induced genomic instability. This was accompanied by evidence of a deregulation of cell cycle progression, such as substantial fold-changes in the expression of proliferating cell nuclear antigen, Cyclin D1, Bcl-2 and Bax genes; and aberrant expression of p53, cyclin A, cyclin E, CDK-2 and aurora kinase-B proteins. Our results demonstrate that MIC in the form of N-succinimidyl N-methylcarbamate promotes germ-line genomic instability in vitro. We envisage that understanding the interplay between environmental toxin-induced signaling and predisposition to testicular cancers would spur identification of meaningful targets for useful therapeutic translational modalities.
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Panwar Hariom, Jain Deepika, Khan Saba, Pathak Neelam, Raghuram Gorantla V., Bhargava Arpit, Banerjee Smita, Mishra Pradyumna K., Imbalance of mitochondrial-nuclear cross talk in isocyanate mediated pulmonary endothelial cell dysfunction, Redox Biology, 1, 1, 2013. Crossref
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Panwar Hariom, Raghuram Gorantla V., Jain Deepika, Ahirwar Alok K., Khan Saba, Jain Subodh K., Pathak Neelam, Banerjee Smita, Maudar Kewal K., Mishra Pradyumna K., Cell cycle deregulation by methyl isocyanate: Implications in liver carcinogenesis, Environmental Toxicology, 29, 3, 2014. Crossref
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Mishra Pradyumna Kumar, Raghuram Gorantla Venkata, Bhargava Arpit, Ahirwar Alok, Samarth Ravindra, Upadhyaya Ravi, Jain Subodh Kumar, Pathak Neelam, In vitroandin vivoevaluation of the anticarcinogenic and cancer chemopreventive potential of a flavonoid-rich fraction from a traditional Indian herbSelaginella bryopteris, British Journal of Nutrition, 106, 8, 2011. Crossref
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Khan Saba, Raghuram Gorantla V., Bhargava Arpit, Pathak Neelam, Chandra Dolly H., Jain Subodh K., Mishra Pradyumna K., Role and clinical significance of lymphocyte mitochondrial dysfunction in type 2 diabetes mellitus, Translational Research, 158, 6, 2011. Crossref
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Bhargava Arpit, Kumari Roshani, Khare Surbhi, Shandilya Ruchita, Gupta Pushpendra Kumar, Tiwari Rajnarayan, Rahman Akhlaqur, Chaudhury Koel, Goryacheva Irina Yu, Mishra Pradyumna Kumar, Mapping the Mitochondrial Regulation of Epigenetic Modifications in Association With Carcinogenic and Noncarcinogenic Polycyclic Aromatic Hydrocarbon Exposure, International Journal of Toxicology, 39, 5, 2020. Crossref
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Bunkar Neha, Sharma Jahnavi, Chouksey Anju, Kumari Roshani, Gupta Pushpendra Kumar, Tiwari Rajnarayan, Lodhi Lalit, Srivastava Rupesh Kumar, Bhargava Arpit, Mishra Pradyumna Kumar, Clostridium perfringens phospholipase C impairs innate immune response by inducing integrated stress response and mitochondrial-induced epigenetic modifications, Cellular Signalling, 75, 2020. Crossref
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Mishra Pradyumna Kumar, Bhargava Arpit, Kumari Roshani, Bunkar Neha, Chauhan Prachi, Mukherjee Suranjana, Shandilya Ruchita, Singh Radha Dutt, Tiwari Rajnarayan, Chaudhury Koel, Integrated mitoepigenetic signalling mechanisms associated with airborne particulate matter exposure: A cross-sectional pilot study, Atmospheric Pollution Research, 13, 5, 2022. Crossref
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Mishra Pradyumna Kumar, Kumari Roshani, Bhargava Arpit, Bunkar Neha, Chauhan Prachi, Tiwari Rajnarayan, Shandilya Ruchita, Srivastava Rupesh Kumar, Singh Radha Dutt, Prenatal exposure to environmental pro-oxidants induces mitochondria-mediated epigenetic changes: a cross-sectional pilot study, Environmental Science and Pollution Research, 2022. Crossref