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Journal of Environmental Pathology, Toxicology and Oncology
Fator do impacto: 1.241 FI de cinco anos: 1.349 SJR: 0.519 SNIP: 0.613 CiteScore™: 1.61

ISSN Imprimir: 0731-8898
ISSN On-line: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.v29.i3.50
pages 213-234

Molecular Characterization of Isocyanate-Induced Male Germ-Line Genomic Instability

Gorantla Venkata Raghuram
Department of Research, Bhopal Memorial Hospital &l Research Centre, Bhokal; and Division of Translational Research, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai, India
Neelam Pathak
Department of Research, Bhopal Memorial Hospital & Research Centre, Bhopal, India
Deepika Jain
Department of Research, Bhopal Memorial Hospital & Research Centre, Bhopal, India
Hemant Pandey
Department of Research, Bhopal Memorial Hospital & Research Centre, Bhopal, India
Hariom Panwar
Department of Biotechnology, Dr. H.S, Gour University, Sagar, India
Subodh Kumar Jain
Department of Biotechnology, Dr. H.S, Gour University, Sagar, India
Smita Banerjee
Department of Biotechnology, Dr. H.S, Gour University, Sagar, India
Pradyumna Kumar Mishra
Department of Research, Bhopal Memorial Hospital & Research Centre, Bhopal; and Division of Translational Research, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai, India

RESUMO

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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