Inflammatory response to isocyanates and onset of genomic instability in cultured human lung fibroblasts

Mishra, Pradyumna Kumar; Bhargava, Arpit; Raghuram, G.; Gupta, Seema; Tiwari, Shaun; Upadhyaya, Ravi; Jain, S. K.; Maudar, K K

doi:10.4238/vol8-1gmr544

Cited by 25 publications

(21 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased p53 activity in response to DNA damage blocks the proliferation of cells in the G1 phase of the cell cycle [48]. In line with this cellular phenomenon, authors' findings in IMR-90, FHC and B/CMBA.Ov cells treated with MIC showed significant cell cycle arrest both at early G1 and G2/M phases, eventually setting the stage for aneuploidy [25,26,47]. These results indicate imbalance in ploidy levels and are probably the response of check-point proteins and interruption of cell cycle progression, due to toxic MIC treatment.…”

Section: Cell Cycle Deregulationmentioning

confidence: 56%

“…Free radicals thus generated impact biochemical component of the cell, with lipids, proteins and nucleic acids being the most important targets. [25,26,34,35,44,46,47]. Our results imply that MIC treatment causes the formation of carcinogen-DNA adducts and induces alterations to DNA ultra-structure.…”

Section: Mitochondrial Retrograde Signalingmentioning

confidence: 57%

“…In this context, the pro-inflammatory cytokine response in human lymphocytes and neutrophils; human lung fibroblasts (IMR-90), human colon epithelial (FHC) cells treated with 0.005 μM (1 μg/μl) MIC were evaluated. Flow cytometric analysis revealed a time-and dose-dependent escalation in the levels of the inflammatory cytokines interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interferon gamma (IFN-γ), IL-8, IL-1β, nuclear transcriptional factor кβ (NF-кβ) and IL-12p70 in culture supernatants of cells studied [24][25][26][27].…”

Section: Chronic Inflammationmentioning

confidence: 99%

See 2 more Smart Citations

Molecular bio-dosimetry for carcinogenic risk assessment in survivors of Bhopal gas tragedy

Mishra¹,

Raghuram²,

Bunkar³

et al. 2015

Int J Occup Med Environ Health

View full text Add to dashboard Cite

International Journal of Occupational Medicine and Environmental AbstractDecember 2014 marked the 30th year anniversary of Bhopal gas tragedy. This sudden and accidental leakage of deadly poisonous methyl isocyanate (MIC) gas instigated research efforts to understand the nature, severity of health damage and sufferings of 570 000 ailing survivors of this tragedy. In a decade-long period, our systematic laboratory investigations coupled with long-term molecular surveillance studies have comprehensively demonstrated that the risk of developing an environmental associated aberrant disease phenotype, including cancer, involves complex interplay of genomic and epigenetic reprogramming. These findings poised us to translate this knowledge into an investigative framework of "molecu lar biodosimetry" in a strictly selected cohort of MIC exposed individuals. A pragmatic cancer risk-assessment strategy pursued in concert with a large-scale epidemiological study might unfold molecular underpinnings of host-susceptibility and exposureresponse relationship. The challenges are enormous, but we postulate that the study will be necessary to establish a direct initiation-promotion paradigm of environmental carcinogenesis. Given that mitochondrial retrograde signaling-induced epigenetic reprogramming is apparently linked to neoplasticity, a cutting-edge tailored approach by an expert pool of biomedical researchers will be fundamental to drive these strategies from planning to execution. Validating the epigenomic signatures will hopefully result in the development of biomarkers to better protect human lives in an overburdened ecosystem, such as India, which is continuously challenged to meet population demands. Besides, delineating the mechanistic links between MIC exposure and cancer morbidity, our investigative strategy might help to formulate suitable regulatory policies and measures to reduce the overall burden of occupational and environmental carcinogenesis.

show abstract

Section: Cell Cycle Deregulationmentioning

confidence: 56%

Section: Mitochondrial Retrograde Signalingmentioning

confidence: 57%

Section: Chronic Inflammationmentioning

confidence: 99%

See 1 more Smart Citation

Molecular bio-dosimetry for carcinogenic risk assessment in survivors of Bhopal gas tragedy

Mishra¹,

Raghuram²,

Bunkar³

et al. 2015

Int J Occup Med Environ Health

View full text Add to dashboard Cite

show abstract

“…Recently, in our preceding study we had reported an enhanced production of inflammatory cytokines upon exposure of immune cells to isocyanates in vitro 28,29) . In addition, in-vitro MIC exposure to lung fibroblast cells was also observed to induce inflammatory response which further leads to genomic instability 30) . In present study, we observed a significant increase in the circulating levels of inflammatory cytokines in group III (MIC exposed group) in comparison to the control group I (control group within Bhopal) and group II (control group outside Bhopal) (Fig.…”

Section: Discussionmentioning

confidence: 99%

Status of Inflammatory Biomarkers in the Population that Survived the Bhopal Gas Tragedy: A Study after Two Decades

et al. 2010

View full text Add to dashboard Cite

“…The cause and genesis of the accident, spectrum of health effects, constituents of the toxic gas cloud and their possible role in the causation of adverse effects are well-debated [7]. Thanks to cellular model systems, the molecular mechanisms underlying the toxico-genomic implications of MIC exposure have now been better understood [8][9][10][11][12]. However, it has been increasingly realized that the study of the human aspect of the tragedy had perhaps been neglected.…”

Section: Introductionmentioning

confidence: 99%

Molecular surveillance of hepatitis and tuberculosis infections in a cohort exposed to methyl isocyanate

Mishra¹,

Bhargava²,

Pathak³

et al. 2011

International Journal of Occupational Medicine and Environmental Health

View full text Add to dashboard Cite

Objective: The potential toxic effects on the immune system exerted by occupational and accidental environmental exposures and underlying molecular regulatory mechanisms involved in the etiology and progression of infectious diseases are now being characterized. The Bhopal gas tragedy is undoubtedly one of the worst industrial disasters in the history of mankind. After 25 years of accidental exposure to methyl isocyanate (MIC), severe systemic ailments still continue to preoccupy the lives of the affected population that survived this tragedy. We have performed a molecular surveillance study to characterize hepatitis and tuberculosis infections amongst the first and the second generation of survivors exposed to MIC. Materials and Methods: Both outdoor and indoor patients referred for molecular diagnosis of hepatitis B virus (HBV), hepatitis C virus (HCV) and Mycobacterium tuberculosis (MTB) were examined. Qualitative analysis for HBsAg, anti-HBc, anti-HCV through ELISA was performed, while BacT/ALERT and Ziehl-Neelson technique were utilized for the assessment of tuberculosis. Detection and quantification of viral and bacterial nucleic acid and characterization of hepatitis genotypes were analyzed using real-time and end-point PCR techniques. Results: The results suggest that HBV infections are most common among the MIC-exposed cohort, followed by extra-pulmonary and pulmonary MTB and HCV infections. Genotype 3 is the most prevalent HCV genotype among the survivors. Failure to detect HBsAg, anti-HBc and anti-HCV through ELISA, and tuberculosis by culture and Ziehl-Neelson stain, indicates higher prevalence of occult hepatitis and latent tuberculosis in the affected population. Conclusions: Our study underscores the importance of hospital-based records used as a data source for monitoring possible environmental health hazards. As the risk of progress of infection is often influenced by conditions and periods of environmental chemical exposure, therefore, insights of interconnected molecular pathways will further illuminate the gene-environment association and might offer valuable information for rational drug design.

show abstract

Inflammatory response to isocyanates and onset of genomic instability in cultured human lung fibroblasts

Cited by 25 publications

References 38 publications

Molecular bio-dosimetry for carcinogenic risk assessment in survivors of Bhopal gas tragedy

Molecular bio-dosimetry for carcinogenic risk assessment in survivors of Bhopal gas tragedy

Status of Inflammatory Biomarkers in the Population that Survived the Bhopal Gas Tragedy: A Study after Two Decades

Molecular surveillance of hepatitis and tuberculosis infections in a cohort exposed to methyl isocyanate

Contact Info

Product

Resources

About