Induction of genomic instability in cultured human colon epithelial cells following exposure to isocyanates.
The toxic response of cultured human colon epithelial-FHC cells to methyl isocyanate was investigated with regard to genomic instability. Qualitative and quantitative assessments of the extent of phosphorylation of DNA damage signaling factors such as ATM, gammaH2AX and p53, was increased in treated cells compared to controls. At the same time, many treated cells were arrested at the G2/M phase of the cell cycle, and had an elevated apoptotic index and increased inflammatory cytokine levels. Cytogenetic analyses revealed varied chromosomal anomalies, with abnormal expression of pericentrin protein. Analysis through ISSR PCR demonstrated increased microsatellite instability. The results imply that isocyanates can cause genomic instability in colonocytes.
Mishra
Pradyumna Kumar
PK
Bhopal Memorial Hospital & Research Centre, Bhopal, India. pkm_8bh@yahoo.co.uk
Bhargava
Arpit
A
Raghuram
Gorantla Venkata
GV
Jatawa
Suresh Kumar
SK
Akhtar
Nabila
N
Khan
Saba
S
Tiwari
Archana
A
Maudar
Kewal Krishan
KK
D000941:Antigens / Q000378:metabolism; D017209:Apoptosis; D002460:Cell Line; D003106:Colon / Q000166:cytology / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D004249:DNA Damage; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D016195:G2 Phase; D042822:Genomic Instability / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D017953:Isocyanates / Q000494:pharmacology*; D007621:Karyotyping; D008677:Metaphase; D015398:Signal Transduction
D000941:Antigens; D016207:Cytokines; D017953:Isocyanates; C086178:pericentrin; C008461:methyl isocyanate